Effectiveness and Safety of Common Non-Oncologic Pharmaceuticals in Cancer Management: A Systematic Review

Authors

  • Luc ZONGO Faculté des Sciences de Santé, Université Saint Thomas d’Aquin (USTA), 06 BP 10212 Ouagadougou 06, Burkina Faso. Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso. https://orcid.org/0000-0002-8886-5142
  • Théodora M. ZOHONCON Faculté des Sciences de Santé, Université Saint Thomas d’Aquin (USTA), 06 BP 10212 Ouagadougou 06, Burkina Faso. Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso.
  • Bakary Tientigui DEMBELE Centre Hospitalier Universitaire Gabriel Touré / FMOS / USTTB, Bamako, Mali.
  • Heiko LANGE NBFC – National Biodiversity Future Center, Piazza Marina, 61, 90133 Palermo, Italy. https://orcid.org/0000-0003-3845-7017
  • Rosemary R. CANFUA Global Access to Affordable Essential Medicines and Safe Alternative Therapies, Kampala, Uganda.
  • Davy P-W BEMBAMBA Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso.
  • Yilédoma T. M. LENGANE Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso.
  • Wilfried F. P. TRAORE Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso.
  • Lucien KABORE Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso.
  • Michel PALUKU MUKULULI Institut Supérieur des Techniques Médicales Lukanga, République Démocratique du Congo.
  • Raogo OUEDRAOGO Université Joseph KI-ZERBO (UJKZ), 03 BP 7021 Ouagadougou 03, Burkina Faso
  • Mimtiri S. ZONGO Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso.
  • Esther Hortence Murielle DINA BELL Faculté de Médecine et des Sciences Pharmaceutiques Université de Doula, Cameroun
  • Modeste W. OUEDRAOGO Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso.
  • Arsène OUEDRAOGO Alicament du Faso’ (ALIFA), 07 BP 5855 Ouagadougou 07, Burkina Faso.
  • Jacques SIMPORE Faculté des Sciences de Santé, Université Saint Thomas d’Aquin (USTA), 06 BP 10212 Ouagadougou 06, Burkina Faso. Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso. https://orcid.org/0000-0002-0415-9161

Abstract

Background. De novo anticancer drug development is lengthy, costly, and risky, motivating cautious evaluation of off-label use of common non-oncologic agents where mechanistic plausibility and clinical signals exist.

Objectives. To synthesize the effectiveness and safety of frequently repurposed non-oncologic drug classes in oncology and to identify priorities for practice and research.

Methods. A PRISMA-guided systematic review (2015–2025) screened titles/abstracts and full texts in duplicate, with standardized extraction and narrative/thematic synthesis. Records identified: 1,699; duplicates removed: 119; other removals (missing metadata): 33; records screened: 1,547; excluded at title/abstract: 956; reports sought: 591; not retrieved: 410; assessed for eligibility: 181; included: 181. Outcomes included OS, PFS/DFS, ORR, QoL, and CTCAE-graded toxicities.

Results. Antihypertensives comprised the largest class, followed by antidiabetics, statins, anti-inflammatories/aspirin, antibiotics, antidepressants, and anthelmintics; lung, breast, colorectal, pancreatic, and ovarian cancers were most represented. Signals suggest possible benefit for overall survival and mortality, with limited and inconsistent evidence for PFS/DFS and ORR; QoL was rarely reported. Outcome definitions, progression ascertainment, censoring rules, exposure metrics (dose, duration, timing), and reporting completeness were heterogeneous, constraining meta-analytic pooling and causal inference.

Conclusion. Generalized repurposing for oncology is not supported at this time beyond established non-oncologic indications. Biologically coherent, low-toxicity signals, most consistently for β-blockade and RAAS modulation, and more variably for metformin, statins, and aspirin, justify targeted, rigorously designed evaluation in prospective trials and robust observational emulations, with harmonized endpoints and systematic CTCAE capture. Equity-by-design, common data elements, preregistration, and data/code sharing are essential to accelerate credible, practice-informing evidence.

Keywords: Non-Oncologic Agents, Effectiveness and Safety, Cancer Management

Keywords:

Non-Oncologic Agents, ffectiveness and Safety, Cancer Management

DOI

https://doi.org/10.22270/jddt.v15i10.7415

Author Biographies

Luc ZONGO , Faculté des Sciences de Santé, Université Saint Thomas d’Aquin (USTA), 06 BP 10212 Ouagadougou 06, Burkina Faso. Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso.

  1. Centre de Recherche Biomoléculaire Pietro Annigoni (CERBA) 01 BP 216 Ouagadougou 01. Burkina Faso.

Théodora M. ZOHONCON, Faculté des Sciences de Santé, Université Saint Thomas d’Aquin (USTA), 06 BP 10212 Ouagadougou 06, Burkina Faso. Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso.

  1. Centre de Recherche Biomoléculaire Pietro Annigoni (CERBA) 01 BP 216 Ouagadougou 01. Burkina Faso.

Bakary Tientigui DEMBELE, Centre Hospitalier Universitaire Gabriel Touré / FMOS / USTTB, Bamako, Mali.

Centre Hospitalier Universitaire Gabriel Touré / FMOS / USTTB, Bamako, Mali.

Heiko LANGE, NBFC – National Biodiversity Future Center, Piazza Marina, 61, 90133 Palermo, Italy.

University of Milano-Bicocca, Department of Earth and Environmental Sciences, Piazza della Scienza 1, 20126 Milan, Italy. 

Rosemary R. CANFUA, Global Access to Affordable Essential Medicines and Safe Alternative Therapies, Kampala, Uganda.

Global Access to Affordable Essential Medicines and Safe Alternative Therapies, Kampala, Uganda.

Davy P-W BEMBAMBA, Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso.

Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso.

Yilédoma T. M. LENGANE, Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso.

Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso.

Wilfried F. P. TRAORE, Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso.

Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso.

Lucien KABORE, Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso.

Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso.

Michel PALUKU MUKULULI, Institut Supérieur des Techniques Médicales Lukanga, République Démocratique du Congo.

Hôpital Adventiste de Mutiri à Butembo, République Démocratique du Congo.

Raogo OUEDRAOGO, Université Joseph KI-ZERBO (UJKZ), 03 BP 7021 Ouagadougou 03, Burkina Faso

Université Joseph KI-ZERBO (UJKZ), 03 BP 7021 Ouagadougou 03, Burkina Faso

Mimtiri S. ZONGO, Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso.

Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso.

Esther Hortence Murielle DINA BELL, Faculté de Médecine et des Sciences Pharmaceutiques Université de Doula, Cameroun

Faculté de Médecine et des Sciences Pharmaceutiques Université de Doula, Cameroun 

Modeste W. OUEDRAOGO, Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso.

Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso.

Arsène OUEDRAOGO, Alicament du Faso’ (ALIFA), 07 BP 5855 Ouagadougou 07, Burkina Faso.

Alicament du Faso’ (ALIFA), 07 BP 5855 Ouagadougou 07, Burkina Faso.

Jacques SIMPORE, Faculté des Sciences de Santé, Université Saint Thomas d’Aquin (USTA), 06 BP 10212 Ouagadougou 06, Burkina Faso. Hôpital Saint Camille de Ouagadougou (HOSCO), 09 BP 444 Ouagadougou 09, Ouagadougou, Burkina Faso.

  1. Centre de Recherche Biomoléculaire Pietro Annigoni (CERBA) 01 BP 216 Ouagadougou 01. Burkina Faso.

References

(1) Wong, C. H.; Siah, K. W.; Lo, A. W. Estimation of Clinical Trial Success Rates and Related Parameters. Biostatistics 2019, 20 (2), 273–286.

(2) DiMasi, J. A.; Grabowski, H. G.; Hansen, R. W. Innovation in the Pharmaceutical Industry: New Estimates of R&D Costs. J. Health Econ. 2016, 47, 20–33.

(3) DiMasi, J. A.; Grabowski, H. G. Economics of New Oncology Drug Development. J. Clin. Oncol. 2007, 25 (2), 209–216. https://doi.org/10.1200/JCO.2006.09.0803.

(4) DiMasi, J. A. Research and Development Costs of New Drugs. Jama 2020, 324 (5), 517–517.

(5) Wouters, O. J.; McKee, M.; Luyten, J. Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009-2018. JAMA 2020, 323 (9), 844–853. https://doi.org/10.1001/jama.2020.1166.

(6) Álvarez, C. A.; Pérez, L. R.; Mateos, M. E. R.; Bautista, M. J. M.; Rodríguez, E. B.; Baena-Cañada, J. M. Off-Label Antineoplastic Drugs. An Effectiveness and Safety Study. Farm. Hosp. 2017, 41 (3), 382–390. https://doi.org/10.7399/fh.2017.41.3.10745.

(7) Drogovoz, S. M.; Starikov, V. I.; Ivantsyk, L. B.; Shchokina, K. G. EXPERIENCE AND PROSPECTS FOR THE USE OF OFF-LABEL DRUGS IN ONCOLOGY. Exp. Oncol. 2023, 43 (1), 1–5. https://doi.org/10.32471/exp-oncology.2312-8852.vol-43-no-1.15583.

(8) Casali, P. G. The Off-Label Use of Drugs in Oncology: A Position Paper by the European Society for Medical Oncology (ESMO). Ann. Oncol. 2007, 18 (12), 1923–1925. https://doi.org/10.1093/annonc/mdm517.

(9) Concato, J. FDA Real-World Evidence Program.

(10) Xie, J.; Xia, L.; Xiang, W.; He, W.; Yin, H.; Wang, F.; Gao, T.; Qi, W.; Yang, Z.; Yang, X.; Zhou, T.; Gao, G. Metformin Selectively Inhibits Metastatic Colorectal Cancer with the KRAS Mutation by Intracellular Accumulation through Silencing MATE1. Proc. Natl. Acad. Sci. U. S. A. 2020, 117 (23), 13012–13022. https://doi.org/10.1073/pnas.1918845117.

(11) Xie, L.-L.; Huang, Y.-B.; Dong, K.-R.; Yang, S.-B.; Shen, C.; Ma, Y.-Y. Postnatal Treatment and Evolution Patterns of Giant Fetal Hepatic Hemangioma: A Case Series of 29 Patients. BMC Pediatr. 2024, 24 (1), 8. https://doi.org/10.1186/s12887-023-04476-2.

(12) Weth, F. R.; Hoggarth, G. B.; Weth, A. F.; Paterson, E.; White, M. P.; Tan, S. T.; Peng, L.; Gray, C. Unlocking Hidden Potential: Advancements, Approaches, and Obstacles in Repurposing Drugs for Cancer Therapy. Br. J. Cancer 2024, 130 (5), 703–715.

(13) Jiang, B.; Li, J.; Chen, J.; Xiang, X.; Xiong, J.; Deng, J. Aortic Dissection in a Patient Treated with Anlotinib for Metastatic Lung Squamous Cell Carcinoma. Thorac. Cancer 2020, 11 (2), 461–464. https://doi.org/10.1111/1759-7714.13288.

(14) Jiang, C.; Zhao, J.; Sun, L.; Cai, B. A Case Report of Rare Ectopic Pheochromocytoma Adjacent to Pancreas. Medicine (Baltimore) 2020, 99 (25), e20858. https://doi.org/10.1097/MD.0000000000020858.

(15) Zaky, M. Y.; Fan, C.; Zhang, H.; Sun, X.-F. Unraveling the Anticancer Potential of Statins: Mechanisms and Clinical Significance. Cancers 2023, 15 (19), 4787.

(16) Braga, P. G. S.; Vieira, J. da S.; Gurgel, A. R. B.; Brum, P. C. β-Blockers and Statins: Exploring the Potential off-Label Applications in Breast, Colorectal, Prostate, and Lung Cancers. Front. Pharmacol. 2024, 15, 1423502.

(17) Fernández-Galván, A.; Rodríguez-Jiménez, P.; González-Sixto, B.; Abalde-Pintos, M. T.; Butrón-Bris, B. Topical and Intralesional Immunotherapy for the Management of Basal Cell Carcinoma. Cancers 2024, 16 (11), 2135.

(18) Liu, R.; Wang, L.; Rizzo, S.; Garmhausen, M. R.; Pal, N.; Waliany, S.; McGough, S.; Lin, Y. G.; Huang, Z.; Neal, J. Systematic Analysis of Off-Label and off-Guideline Cancer Therapy Usage in a Real-World Cohort of 165,912 US Patients. Cell Rep. Med. 2024, 5 (3).

(19) Iduh, M. U.; Imam, U. A.; BunzaMuhammad, N.; Enitan, S. S.; Hassan, Y. Mechanism of Antimicrobial Activities of Medicinal Plants Extracts, From Traditional Knowledge to Scientific Insights.

(20) Gutiérrez-Pacheco, M. M.; Torres-Moreno, H.; Flores-Lopez, M. L.; Velázquez Guadarrama, N.; Ayala-Zavala, J. F.; Ortega-Ramírez, L. A.; López-Romero, J. C. Mechanisms and Applications of Citral’s Antimicrobial Properties in Food Preservation and Pharmaceuticals Formulations. Antibiotics 2023, 12 (11), 1608.

(21) Mansoori, S.; Fryknäs, M.; Alvfors, C.; Loskog, A.; Larsson, R.; Nygren, P. A Phase 2a Clinical Study on the Safety and Efficacy of Individualized Dosed Mebendazole in Patients with Advanced Gastrointestinal Cancer. Sci. Rep. 2021, 11 (1), 8981. https://doi.org/10.1038/s41598-021-88433-y.

(22) Harris, J.; Phillips, J. D. Evaluating the Clinical Outcomes of Parotid Hemangiomas in the Pediatric Patient Population. Ear. Nose. Throat J. 2021, 100 (5), NP242–NP245. https://doi.org/10.1177/0145561319877760.

(23) Olsen, G. M.; Hansen, L. M.; Stefanko, N. S.; Mathes, E.; Puttgen, K. B.; Tollefson, M. M.; Lauren, C.; Mancini, A. J.; McCuaig, C. C.; Frieden, I. J.; Adams, D.; Baselga, E.; Chamlin, S.; Gupta, D.; Frommelt, P.; Garzon, M. C.; Horii, K.; Klajn, J.; Maheshwari, M.; Newell, B.; Nguyen, H. L.; Nopper, A.; Powell, J.; Siegel, D. H.; Drolet, B. A. Evaluating the Safety of Oral Propranolol Therapy in Patients With PHACE Syndrome. JAMA Dermatol. 2020, 156 (2), 186–190. https://doi.org/10.1001/jamadermatol.2019.3839.

(24) Everatt, R.; Kuzmickienė, I.; Brasiūnienė, B.; Vincerževskienė, I.; Intaitė, B.; Cicėnas, S.; Lisauskienė, I. Evaluation of Antihypertensive Medications Use and Survival in Patients with Ovarian Cancer: A Population-Based Retrospective Cohort Study. BMC Womens Health 2024, 24 (1), 155. https://doi.org/10.1186/s12905-024-02983-7.

(25) Knight, J. M.; Kerswill, S. A.; Hari, P.; Cole, S. W.; Logan, B. R.; D’Souza, A.; Shah, N. N.; Horowitz, M. M.; Stolley, M. R.; Sloan, E. K.; Giles, K. E.; Costanzo, E. S.; Hamadani, M.; Chhabra, S.; Dhakal, B.; Rizzo, J. D. Repurposing Existing Medications as Cancer Therapy: Design and Feasibility of a Randomized Pilot Investigating Propranolol Administration in Patients Receiving Hematopoietic Cell Transplantation. BMC Cancer 2018, 18 (1), 593. https://doi.org/10.1186/s12885-018-4509-0.

(26) Montoya, A.; Amaya, C. N.; Belmont, A.; Diab, N.; Trevino, R.; Villanueva, G.; Rains, S.; Sanchez, L. A.; Badri, N.; Otoukesh, S.; Khammanivong, A.; Liss, D.; Baca, S. T.; Aguilera, R. J.; Dickerson, E. B.; Torabi, A.; Dwivedi, A. K.; Abbas, A.; Chambers, K.; Bryan, B. A.; Nahleh, Z. Use of Non-Selective β-Blockers Is Associated with Decreased Tumor Proliferative Indices in Early Stage Breast Cancer. Oncotarget 2017, 8 (4), 6446–6460. https://doi.org/10.18632/oncotarget.14119.

(27) Cai, D.; Sun, H.; Qi, Y.; Zhao, X.; Feng, M.; Wu, X. Insulin-Like Growth Factor 1/Mammalian Target of Rapamycin and AMP-Activated Protein Kinase Signaling Involved in the Effects of Metformin in the Human Endometrial Cancer. Int. J. Gynecol. Cancer Off. J. Int. Gynecol. Cancer Soc. 2016, 26 (9), 1667–1672. https://doi.org/10.1097/IGC.0000000000000818.

(28) Cuyàs, E.; Fernández-Arroyo, S.; Buxó, M.; Pernas, S.; Dorca, J.; Álvarez, I.; Martínez, S.; Pérez-Garcia, J. M.; Batista-López, N.; Rodríguez-Sánchez, C. A.; Amillano, K.; Domínguez, S.; Luque, M.; Morilla, I.; Stradella, A.; Viñas, G.; Cortés, J.; Verdura, S.; Brunet, J.; López-Bonet, E.; Garcia, M.; Saidani, S.; Joven, J.; Martin-Castillo, B.; Menendez, J. A. Metformin Induces a Fasting- and Antifolate-Mimicking Modification of Systemic Host Metabolism in Breast Cancer Patients. Aging 2019, 11 (9), 2874–2888. https://doi.org/10.18632/aging.101960.

(29) Nanni, O.; Amadori, D.; De Censi, A.; Rocca, A.; Freschi, A.; Bologna, A.; Gianni, L.; Rosetti, F.; Amaducci, L.; Cavanna, L.; Foca, F.; Sarti, S.; Serra, P.; Valmorri, L.; Bruzzi, P.; Corradengo, D.; Gennari, A.; MYME investigators. Metformin plus Chemotherapy versus Chemotherapy Alone in the First-Line Treatment of HER2-Negative Metastatic Breast Cancer. The MYME Randomized, Phase 2 Clinical Trial. Breast Cancer Res. Treat. 2019, 174 (2), 433–442. https://doi.org/10.1007/s10549-018-05070-2.

(30) Murff, H. J.; Roumie, C. L.; Greevy, R. A.; Hackstadt, A. J.; McGowan, L. E. D.; Hung, A. M.; Grijalva, C. G.; Griffin, M. R. Metformin Use and Incidence Cancer Risk: Evidence for a Selective Protective Effect against Liver Cancer. Cancer Causes Control CCC 2018, 29 (9), 823–832. https://doi.org/10.1007/s10552-018-1058-4.

(31) Yuan, L.; Bing, Z.; Han, J.; An, X.; Liu, X.; Li, R.; Wang, C.; Sun, X.; Yang, L.; Yang, K. Study on the Anti-Tumor Mechanism Related to Immune Microenvironment of Bombyx Batryticatus on Viral and Non-Viral Infections of Hepatocellular Carcinoma. Biomed. Pharmacother. Biomedecine Pharmacother. 2020, 124, 109838. https://doi.org/10.1016/j.biopha.2020.109838.

(32) Park, Y.-M. M.; White, A. J.; Nichols, H. B.; O’Brien, K. M.; Weinberg, C. R.; Sandler, D. P. The Association between Metabolic Health, Obesity Phenotype and the Risk of Breast Cancer. Int. J. Cancer 2017, 140 (12), 2657–2666. https://doi.org/10.1002/ijc.30684.

(33) Uehara, S.; Sato, K. K.; Koh, H.; Shibata, M.; Kinuhata, S.; Yamada, A.; Oue, K.; Kambe, H.; Morimoto, M.; Hayashi, T. The Association Between Metabolically Healthy Obesity and the Risk of Proteinuria: The Kansai Healthcare Study. J. Epidemiol. 2018, 28 (8), 361–366. https://doi.org/10.2188/jea.JE20170082.

(34) Howells, L. M.; Mahale, J.; Smagurauskaite, G.; Brown, K.; Thomas, A. The Role of Stromal Fibroblasts in Lung Carcinogenesis: A Target for Chemoprevention? 2015.

(35) Siracusa, R. Neuroinflammation and Oxidative Stress in the Traumatic Brain Injury and in the Pathogenesis of Neurodegenerative Diseases: Modulation by Nutritional Supplementation. 2020.

(36) Le Roy, A.; Prébet, T.; Castellano, R.; Goubard, A.; Riccardi, F.; Fauriat, C.; Granjeaud, S.; Benyamine, A.; Castanier, C.; Orlanducci, F.; Ben Amara, A.; Pont, F.; Fournié, J.-J.; Collette, Y.; Mege, J.-L.; Vey, N.; Olive, D. Immunomodulatory Drugs Exert Anti-Leukemia Effects in Acute Myeloid Leukemia by Direct and Immunostimulatory Activities. Front. Immunol. 2018, 9, 977. https://doi.org/10.3389/fimmu.2018.00977.

(37) Furman, J. L.; Norris, C. M. Calcineurin and Glial Signaling: Neuroinflammation and Beyond. J. Neuroinflammation 2014, 11 (1), 158. https://doi.org/10.1186/s12974-014-0158-7.

(38) Cairat, M.; Pottegård, A.; Olesen, M.; Dossus, L.; Fournier, A.; Hicks, B. Antiplatelet Drugs and Breast Cancer Risk in a Large Nationwide Danish Case-Control Study. Int. J. Cancer 2023, 152 (7), 1337–1347. https://doi.org/10.1002/ijc.34343.

(39) Restivo, A.; Cocco, I. M. F.; Casula, G.; Scintu, F.; Cabras, F.; Scartozzi, M.; Zorcolo, L. Aspirin as a Neoadjuvant Agent during Preoperative Chemoradiation for Rectal Cancer. Br. J. Cancer 2015, 113 (8), 1133–1139. https://doi.org/10.1038/bjc.2015.336.

(40) Matsuo, K.; Cahoon, S. S.; Yoshihara, K.; Shida, M.; Kakuda, M.; Adachi, S.; Moeini, A.; Machida, H.; Garcia-Sayre, J.; Ueda, Y.; Enomoto, T.; Mikami, M.; Roman, L. D.; Sood, A. K. Association of Low-Dose Aspirin and Survival of Women With Endometrial Cancer. Obstet. Gynecol. 2016, 128 (1), 127–137. https://doi.org/10.1097/AOG.0000000000001491.

(41) Frouws, M. A.; Bastiaannet, E.; Langley, R. E.; Chia, W. K.; van Herk-Sukel, M. P. P.; Lemmens, V. E. P. P.; Putter, H.; Hartgrink, H. H.; Bonsing, B. A.; Van de Velde, C. J. H.; Portielje, J. E. A.; Liefers, G. J. Effect of Low-Dose Aspirin Use on Survival of Patients with Gastrointestinal Malignancies; an Observational Study. Br. J. Cancer 2017, 116 (3), 405–413. https://doi.org/10.1038/bjc.2016.425.

(42) Jiang, W.; Wang, L.; Zhang, J.; Shen, H.; Dong, W.; Zhang, T.; Li, X.; Wang, K.; Du, J. Effects of Postoperative Non-Steroidal Anti-Inflammatory Drugs on Long-Term Survival and Recurrence of Patients with Non-Small Cell Lung Cancer. Medicine (Baltimore) 2018, 97 (39), e12442. https://doi.org/10.1097/MD.0000000000012442.

(43) Ralph, S. J.; Pritchard, R.; Rodríguez-Enríquez, S.; Moreno-Sánchez, R.; Ralph, R. K. Hitting the Bull’s-Eye in Metastatic Cancers—NSAIDs Elevate ROS in Mitochondria, Inducing Malignant Cell Death. Pharmaceuticals 2015, 8 (1), 62–106.

(44) Rajabu, H. N.; Hinderaker, S. G.; Mnandi, P.; Mutagonda, R. F. Prevalence of Renal Insufficiency and Factors Associated among Selected Cancer Patients on Chemotherapy at Ocean Road Cancer Institute in Tanzania: A Cross-Sectional Study. BMC Cancer 2024, 24 (1), 763. https://doi.org/10.1186/s12885-024-12419-y.

(45) Chuang, M.-C.; Yang, Y.-H.; Hsieh, M.-J.; Lin, Y.-C.; Yang, T.-M.; Chen, P.-C.; Hung, M.-S. The Association of Aspirin Use with Overall Survival of Patients with Inoperable Non-Small Cell Lung Cancer: A Retrospective Study. BMC Cancer 2021, 21 (1), 1257. https://doi.org/10.1186/s12885-021-08999-8.

(46) Kuderer, N. M.; Choueiri, T. K.; Shah, D. P.; Shyr, Y.; Rubinstein, S. M.; Rivera, D. R.; Shete, S.; Hsu, C.-Y.; Desai, A.; de Lima Lopes, G.; Grivas, P.; Painter, C. A.; Peters, S.; Thompson, M. A.; Bakouny, Z.; Batist, G.; Bekaii-Saab, T.; Bilen, M. A.; Bouganim, N.; Larroya, M. B.; Castellano, D.; Del Prete, S. A.; Doroshow, D. B.; Egan, P. C.; Elkrief, A.; Farmakiotis, D.; Flora, D.; Galsky, M. D.; Glover, M. J.; Griffiths, E. A.; Gulati, A. P.; Gupta, S.; Hafez, N.; Halfdanarson, T. R.; Hawley, J. E.; Hsu, E.; Kasi, A.; Khaki, A. R.; Lemmon, C. A.; Lewis, C.; Logan, B.; Masters, T.; McKay, R. R.; Mesa, R. A.; Morgans, A. K.; Mulcahy, M. F.; Panagiotou, O. A.; Peddi, P.; Pennell, N. A.; Reynolds, K.; Rosen, L. R.; Rosovsky, R.; Salazar, M.; Schmidt, A.; Shah, S. A.; Shaya, J. A.; Steinharter, J.; Stockerl-Goldstein, K. E.; Subbiah, S.; Vinh, D. C.; Wehbe, F. H.; Weissmann, L. B.; Wu, J. T.-Y.; Wulff-Burchfield, E.; Xie, Z.; Yeh, A.; Yu, P. P.; Zhou, A. Y.; Zubiri, L.; Mishra, S.; Lyman, G. H.; Rini, B. I.; Warner, J. L.; COVID-19 and Cancer Consortium. Clinical Impact of COVID-19 on Patients with Cancer (CCC19): A Cohort Study. Lancet Lond. Engl. 2020, 395 (10241), 1907–1918. https://doi.org/10.1016/S0140-6736(20)31187-9.

(47) Hirashima, T.; Tamura, Y.; Han, Y.; Hashimoto, S.; Tanaka, A.; Shiroyama, T.; Morishita, N.; Suzuki, H.; Okamoto, N.; Akada, S.; Fujishima, M.; Kadota, Y.; Sakata, K.; Nishitani, A.; Miyazaki, S.; Nagai, T. Efficacy and Safety of Concurrent Anti-Cancer and Anti-Tuberculosis Chemotherapy in Cancer Patients with Active Mycobacterium Tuberculosis: A Retrospective Study. BMC Cancer 2018, 18 (1), 975. https://doi.org/10.1186/s12885-018-4889-1.

(48) Shukla, T.; Smith, S.; Johnstone, K.; Donald, P.; Hanson, J. The Characteristics and Clinical Course of Patients with Melioidosis and Cancer. PLoS Negl. Trop. Dis. 2024, 18 (10), e0012631. https://doi.org/10.1371/journal.pntd.0012631.

(49) Yu, Z.; Dee, E. C.; Bach, D. Q.; Mostaghimi, A.; LeBoeuf, N. R. Evaluation of a Comprehensive Skin Toxicity Program for Patients Treated With Epidermal Growth Factor Receptor Inhibitors at a Cancer Treatment Center. JAMA Dermatol. 2020, 156 (10), 1079–1085. https://doi.org/10.1001/jamadermatol.2020.1795.

(50) Spada, F.; Pellicori, S.; Zampino, G.; Funicelli, L.; Gervaso, L.; Laffi, A.; Rubino, M.; Garcia-Carbonero, R.; Fazio, N. SARS-CoV-2-Related Pneumonia Can Be Successfully Managed in Patients with Metastatic Neuroendocrine Tumors: A Critical Point of View. Endocrine 2020, 70 (1), 6–10. https://doi.org/10.1007/s12020-020-02419-w.

(51) Schmidt, L.; Baskaran, S.; Johansson, P.; Padhan, N.; Matuszewski, D.; Green, L. C.; Elfineh, L.; Wee, S.; Häggblad, M.; Martens, U.; Westermark, B.; Forsberg-Nilsson, K.; Uhrbom, L.; Claesson-Welsh, L.; Andäng, M.; Sintorn, I.-M.; Lundgren, B.; Lönnstedt, I.; Krona, C.; Nelander, S. Case-Specific Potentiation of Glioblastoma Drugs by Pterostilbene. Oncotarget 2016, 7 (45), 73200–73215. https://doi.org/10.18632/oncotarget.12298.

(52) Nakajima, Y.; Kuribayashi, K.; Tada, A.; Nagano, A.; Minami, T.; Kanehiro, A.; Kijima, T. Enhancing Duloxetine With Mirogabalin for Treating Taxane-Induced Peripheral Neuropathy in Advanced Lung Cancer. Cancer Control J. Moffitt Cancer Cent. 2025, 32, 10732748251353327. https://doi.org/10.1177/10732748251353327.

(53) Bernsen, E. C.; Verwiel, E. T. P.; van der Lee, M.; Swen, J. J.; Santoso, M.; Brigitha, L. J.; Admiraal, R.; Tops, B. B. J.; Huitema, A. D. R.; Kemmeren, P.; Hehir-Kwa, J. Y.; Hanff, L. M.; Diekstra, M. H. M. Implementing Pre-Emptive Pharmacogenetics: Impact of Early Pharmacogenetic Screening in a Pediatric Oncology Cohort of 1,151 Subjects. Clin. Pharmacol. Ther. 2025, 118 (2), 438–448. https://doi.org/10.1002/cpt.3685.

(54) Hiramoto, S.; Asano, H.; Miyamoto, T.; Takegami, M.; Kawabata, A. Risk Factors and Pharmacotherapy for Chemotherapy-Induced Peripheral Neuropathy in Paclitaxel-Treated Female Cancer Survivors: A Retrospective Study in Japan. PloS One 2021, 16 (12), e0261473. https://doi.org/10.1371/journal.pone.0261473.

(55) Sandoval, M. A.; Pagsisihan, D.; Berberabe, A.; Palugod-Lopez, E. G. A Malignant Cause of Hypoglycaemia: A Metastatic Insulin-Secreting Pancreatic Neuroendocrine Carcinoma. BMJ Case Rep. 2016, 2016, bcr2016214702. https://doi.org/10.1136/bcr-2016-214702.

(56) Ki, Y.-J.; Kim, H. J.; Kim, M.-S.; Park, C. M.; Ko, M. J.; Seo, Y. S.; Moon, S. M.; Choi, J. A. Association between Metformin Use and Survival in Nonmetastatic Rectal Cancer Treated with a Curative Resection: A Nationwide Population Study. Cancer Res. Treat. 2017, 49 (1), 29–36. https://doi.org/10.4143/crt.2016.128.

(57) Seo, Y.-S.; Kim, Y.-J.; Kim, M.-S.; Suh, K.-S.; Kim, S. B.; Han, C. J.; Kim, Y. J.; Jang, W. I.; Kang, S. H.; Tchoe, H. J.; Park, C. M.; Jo, A. J.; Kim, H. J.; Choi, J. A.; Choi, H. J.; Polak, M. N.; Ko, M. J. Association of Metformin Use With Cancer-Specific Mortality in Hepatocellular Carcinoma After Curative Resection: A Nationwide Population-Based Study. Medicine (Baltimore) 2016, 95 (17), e3527. https://doi.org/10.1097/MD.0000000000003527.

(58) Yendamuri, S.; Barbi, J.; Pabla, S.; Petrucci, C.; Punnanitinont, A.; Nesline, M.; Glenn, S. T.; Depietro, P.; Papanicalou-Sengos, A.; Morrison, C.; Dy, G. K.; Elkin, P. L. Body Mass Index Influences the Salutary Effects of Metformin on Survival After Lobectomy for Stage I NSCLC. J. Thorac. Oncol. Off. Publ. Int. Assoc. Study Lung Cancer 2019, 14 (12), 2181–2187. https://doi.org/10.1016/j.jtho.2019.07.020.

(59) Chin, R. T.; Kiew, J. J.; Ho, K. Y.; Deepak, D. S. Case Report: Diazoxide-Induced Diabetic Ketoacidosis in a Patient with Insulinoma. Front. Endocrinol. 2025, 16, 1524288. https://doi.org/10.3389/fendo.2025.1524288.

(60) Madan, R.; Mettler, T.; Froelich, J.; Chow, L. S. Changing Insulinoma Management Due to Incidentally Discovered Metastasis: A Case Report. Am. J. Case Rep. 2020, 21, e923356. https://doi.org/10.12659/AJCR.923356.

(61) Niitsu, Y.; Minami, I.; Izumiyama, H.; Hashimoto, K.; Yoshimoto, T.; Satou, F.; Tsujino, M.; Ota, K.; Kudo, A.; Tanabe, M.; Yamada, T.; Ogawa, Y. Clinical Outcomes of 20 Japanese Patients with Insulinoma Treated with Diazoxide. Endocr. J. 2019, 66 (2), 149–155. https://doi.org/10.1507/endocrj.EJ18-0353.

(62) Guadagni, F.; Riondino, S.; Formica, V.; Del Monte, G.; Morelli, A. M.; Lucchetti, J.; Spila, A.; D’Alessandro, R.; Della-Morte, D.; Ferroni, P.; Roselli, M. Clinical Significance of Glycemic Parameters on Venous Thromboembolism Risk Prediction in Gastrointestinal Cancer. World J. Gastroenterol. 2017, 23 (28), 5187–5195. https://doi.org/10.3748/wjg.v23.i28.5187.

(63) Aida, A.; Noto, H. Diagnosis and Treatment Course of Insulinoma Presenting as Hypoglycemia Unawareness Using a Factory-Calibrated Continuous Glucose Monitoring System. Am. J. Case Rep. 2022, 23, e936723. https://doi.org/10.12659/AJCR.936723.

(64) Ramos-Peñafiel, C.; Olarte-Carrillo, I.; Cerón-Maldonado, R.; Rozen-Fuller, E.; Kassack-Ipiña, J. J.; Meléndez-Mier, G.; Collazo-Jaloma, J.; Martínez-Tovar, A. Effect of Metformin on the Survival of Patients with ALL Who Express High Levels of the ABCB1 Drug Resistance Gene. J. Transl. Med. 2018, 16 (1), 245. https://doi.org/10.1186/s12967-018-1620-6.

(65) Fontana, L.; Villareal, D. T.; Das, S. K.; Smith, S. R.; Meydani, S. N.; Pittas, A. G.; Klein, S.; Bhapkar, M.; Rochon, J.; Ravussin, E.; Holloszy, J. O.; CALERIE Study Group. Effects of 2-Year Calorie Restriction on Circulating Levels of IGF-1, IGF-Binding Proteins and Cortisol in Nonobese Men and Women: A Randomized Clinical Trial. Aging Cell 2016, 15 (1), 22–27. https://doi.org/10.1111/acel.12400.

(66) Chew, G. M.; Padua, A. J. P.; Chow, D. C.; Souza, S. A.; Clements, D. M.; Corley, M. J.; Pang, A. P. S.; Alejandria, M. M.; Gerschenson, M.; Shikuma, C. M.; Ndhlovu, L. C. Effects of Brief Adjunctive Metformin Therapy in Virologically Suppressed HIV-Infected Adults on Polyfunctional HIV-Specific CD8 T Cell Responses to PD-L1 Blockade. AIDS Res. Hum. Retroviruses 2021, 37 (1), 24–33. https://doi.org/10.1089/AID.2020.0172.

(67) Scarton, L.; Jo, A.; Xie, Z.; O’Neal, L. J.; Munoz Pena, J. M.; George, T. J.; Bian, J. Examining the Relationship between Metformin Dose and Cancer Survival: A SEER-Medicare Analysis. PloS One 2022, 17 (10), e0275681. https://doi.org/10.1371/journal.pone.0275681.

(68) Biben, E.; Menon, L.; Gokden, N.; Spond, M. F.; Eichhorn, J. M.; Aydin, A. M. Giant Left Pheochromocytoma with Vascular Anomalies and Pelvic Horseshoe Kidney: A Case Report. BMC Urol. 2023, 23 (1), 204. https://doi.org/10.1186/s12894-023-01370-y.

(69) Cho, W.-R.; Wang, C.-C.; Tsai, M.-Y.; Chou, C.-K.; Liu, Y.-W.; Wu, Y.-J.; Lin, M.-T.; Chen, K.-D.; Chuang, C.-H.; Huang, P.-Y.; Hu, T.-H.; Tsai, M.-C. Impact of Metformin Use on the Recurrence of Hepatocellular Carcinoma after Initial Liver Resection in Diabetic Patients. PloS One 2021, 16 (3), e0247231. https://doi.org/10.1371/journal.pone.0247231.

(70) Liu, L.; Wang, H.; Cui, J.; Zhang, Q.; Zhang, W.; Xu, W.; Lu, H.; Liu, S.; Shen, S.; Fang, F.; Li, L.; Yang, W.; Zhuang, Z.; Li, J. Inhibition of Protein Phosphatase 2A Sensitizes Mucoepidermoid Carcinoma to Chemotherapy via the PI3K-AKT Pathway in Response to Insulin Stimulus. Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol. 2018, 50 (1), 317–331. https://doi.org/10.1159/000494008.

(71) Wang, W.-M.; Yang, S.-S.; Shao, S.-H.; Nie, H.-Q.; Zhang, J.; Su, T. Metformin Downregulates the Expression of Epidermal Growth Factor Receptor Independent of Lowering Blood Glucose in Oral Squamous Cell Carcinoma. Front. Endocrinol. 2022, 13, 828608. https://doi.org/10.3389/fendo.2022.828608.

(72) Moro, M.; Caiola, E.; Ganzinelli, M.; Zulato, E.; Rulli, E.; Marabese, M.; Centonze, G.; Busico, A.; Pastorino, U.; de Braud, F. G.; Vernieri, C.; Simbolo, M.; Bria, E.; Scarpa, A.; Indraccolo, S.; Broggini, M.; Sozzi, G.; Garassino, M. C. Metformin Enhances Cisplatin-Induced Apoptosis and Prevents Resistance to Cisplatin in Co-Mutated KRAS/LKB1 NSCLC. J. Thorac. Oncol. Off. Publ. Int. Assoc. Study Lung Cancer 2018, 13 (11), 1692–1704. https://doi.org/10.1016/j.jtho.2018.07.102.

(73) Winters, B.; Plymate, S.; Zeliadt, S. B.; Holt, S.; Zhang, X.; Hu, E.; Lin, D. W.; Morrissey, C.; Wooldridge, B.; Gore, J. L.; Porter, M. P.; Wright, J. L. Metformin Effects on Biochemical Recurrence and Metabolic Signaling in the Prostate. The Prostate 2015, 75 (15), 1694–1703. https://doi.org/10.1002/pros.23049.

(74) Oh, B. Y.; Park, Y. A.; Huh, J. W.; Cho, Y. B.; Yun, S. H.; Lee, W. Y.; Park, H. C.; Choi, D. H.; Park, Y. S.; Kim, H. C. Metformin Enhances the Response to Radiotherapy in Diabetic Patients with Rectal Cancer. J. Cancer Res. Clin. Oncol. 2016, 142 (6), 1377–1385. https://doi.org/10.1007/s00432-016-2148-x.

(75) Paulus, J. K.; Williams, C. D.; Cossor, F. I.; Kelley, M. J.; Martell, R. E. Metformin, Diabetes, and Survival among U.S. Veterans with Colorectal Cancer. Cancer Epidemiol. Biomark. Prev. Publ. Am. Assoc. Cancer Res. Cosponsored Am. Soc. Prev. Oncol. 2016, 25 (10), 1418–1425. https://doi.org/10.1158/1055-9965.EPI-16-0312.

(76) Kim, Y.; Vagia, E.; Viveiros, P.; Kang, C. Y.; Lee, J. Y.; Gim, G.; Cho, S.; Choi, H.; Kim, L.; Park, I.; Choi, J.; Chae, Y. K. Overcoming Acquired Resistance to PD-1 Inhibitor with the Addition of Metformin in Small Cell Lung Cancer (SCLC). Cancer Immunol. Immunother. CII 2021, 70 (4), 961–965. https://doi.org/10.1007/s00262-020-02703-8.

(77) Higuchi, T.; Yamamoto, J.; Sugisawa, N.; Tashiro, Y.; Nishino, H.; Yamamoto, N.; Hayashi, K.; Kimura, H.; Miwa, S.; Igarashi, K.; Bouvet, M.; Singh, S. R.; Tsuchiya, H.; Hoffman, R. M. PPARγ Agonist Pioglitazone in Combination With Cisplatinum Arrests a Chemotherapy-Resistant Osteosarcoma PDOX Model. Cancer Genomics Proteomics 2020, 17 (1), 35–40. https://doi.org/10.21873/cgp.20165.

(78) Maraka, S.; Groves, M. D.; Mammoser, A. G.; Melguizo-Gavilanes, I.; Conrad, C. A.; Tremont-Lukats, I. W.; Loghin, M. E.; O’Brien, B. J.; Puduvalli, V. K.; Sulman, E. P.; Hess, K. R.; Aldape, K. D.; Gilbert, M. R.; de Groot, J. F.; Alfred Yung, W. K.; Penas-Prado, M. Phase 1 Lead-in to a Phase 2 Factorial Study of Temozolomide plus Memantine, Mefloquine, and Metformin as Postradiation Adjuvant Therapy for Newly Diagnosed Glioblastoma. Cancer 2019, 125 (3), 424–433. https://doi.org/10.1002/cncr.31811.

(79) Fernandez, C.; Rysä, J.; Almgren, P.; Nilsson, J.; Engström, G.; Orho-Melander, M.; Ruskoaho, H.; Melander, O. Plasma Levels of the Proprotein Convertase Furin and Incidence of Diabetes and Mortality. J. Intern. Med. 2018, 284 (4), 377–387. https://doi.org/10.1111/joim.12783.

(80) Xu, T.; Li, D.; He, Y.; Zhang, F.; Qiao, M.; Chen, Y. Prognostic Value of Metformin for Non-Small Cell Lung Cancer Patients with Diabetes. World J. Surg. Oncol. 2018, 16 (1), 60. https://doi.org/10.1186/s12957-018-1362-1.

(81) Hong, Y.; Lee, S.; Won, S. The Preventive Effect of Metformin on Progression of Benign Prostate Hyperplasia: A Nationwide Population-Based Cohort Study in Korea. PloS One 2019, 14 (7), e0219394. https://doi.org/10.1371/journal.pone.0219394.

(82) Dworacki, G.; Urazayev, O.; Bekmukhambetov, Y.; Iskakova, S.; Frycz, B. A.; Jagodziński, P. P.; Dworacka, M. Thymic Emigration Patterns in Patients with Type 2 Diabetes Treated with Metformin. Immunology 2015, 146 (3), 456–469. https://doi.org/10.1111/imm.12522.

(83) Adarsh, M.; Salman, M.; Kumar, M. S.; Shetty, M. Unusual Presentation of an Insulinoma in an Elderly Male Patient. J. Postgrad. Med. 2021, 67 (3), 164–167. https://doi.org/10.4103/jpgm.JPGM_1165_20.

(84) Gillessen, S.; Murphy, L.; James, N. D.; Sachdeva, A.; El-Taji, O.; Abdel-Aty, H.; Adler, A. I.; Amos, C.; Attard, G.; Varughese, M.; Gale, J.; Brown, S.; Srihari, N.; Birtle, A. J.; Brown, M.; Chan, K.; Chowdhury, S.; Cross, W.; Dearnaley, D. P.; Din, O.; Dutey-Magni, P.; Gilbert, D. C.; Gilson, C.; Gray, S.; Grist, E.; Hofmann, U.; Hudson, A. M.; Jain, Y.; Jeyasangar, G.; Jones, R.; Kayani, M.; Langley, R. E.; Malik, Z.; Mason, M. D.; Matheson, D.; McAlpine, C.; Macnair, A.; Millman, R.; Murphy, C.; Padden-Modi, M.; Parikh, O.; Parker, C.; Rush, H.; Russell, M.; Srinivasan, R.; Sundar, S.; Tanguay, J. S.; Turco, F.; Williams, P.; Sydes, M. R.; Parmar, M. K. B.; Brown, L. C.; Clarke, N. W.; STAMPEDE investigators. Metformin for Patients with Metastatic Prostate Cancer Starting Androgen Deprivation Therapy: A Randomised Phase 3 Trial of the STAMPEDE Platform Protocol. Lancet Oncol. 2025, 26 (8), 1018–1030. https://doi.org/10.1016/S1470-2045(25)00231-1.

(85) Marrone, K. A.; Zhou, X.; Forde, P. M.; Purtell, M.; Brahmer, J. R.; Hann, C. L.; Kelly, R. J.; Coleman, B.; Gabrielson, E.; Rosner, G. L.; Ettinger, D. S. A Randomized Phase II Study of Metformin plus Paclitaxel/Carboplatin/Bevacizumab in Patients with Chemotherapy-Naïve Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer. The Oncologist 2018, 23 (7), 859–865. https://doi.org/10.1634/theoncologist.2017-0465.

(86) Matsuo, K.; Gualtieri, M. R.; Cahoon, S. S.; Toboni, M. D.; Machida, H.; Moeini, A.; Hasegawa, K.; Shoupe, D.; Roman, L. D. Contributing Factors for Menopausal Symptoms after Surgical Staging for Endometrial Cancer. Menopause N. Y. N 2016, 23 (5), 535–543. https://doi.org/10.1097/GME.0000000000000576.

(87) Broekman, K. E.; Hof, M. A. J.; Touw, D. J.; Gietema, J. A.; Nijman, H. W.; Lefrandt, J. D.; Reyners, A. K. L.; Jalving, M. Phase I Study of Metformin in Combination with Carboplatin/Paclitaxel Chemotherapy in Patients with Advanced Epithelial Ovarian Cancer. Invest. New Drugs 2020, 38 (5), 1454–1462. https://doi.org/10.1007/s10637-020-00920-7.

(88) Stokes, W. A.; Eguchi, M.; Amini, A.; Hararah, M. K.; Ding, D.; McDermott, J. D.; Bradley, C. J.; Karam, S. D. Survival Impact and Toxicity of Metformin in Head and Neck Cancer: An Analysis of the SEER-Medicare Dataset. Oral Oncol. 2018, 84, 12–19. https://doi.org/10.1016/j.oraloncology.2018.06.022.

(89) van Londen, M.; Roosma, E.; Vogels, S.; van Putten, J. W. G.; Janssen, W. M. T. Acute Kidney Injury and Long-Term Renal Effects of Alectinib in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Carcinoma: A Case Report. J. Med. Case Reports 2022, 16 (1), 347. https://doi.org/10.1186/s13256-022-03532-2.

(90) Morris, Z. S.; Saha, S.; Magnuson, W. J.; Morris, B. A.; Borkenhagen, J. F.; Ching, A.; Hirose, G.; McMurry, V.; Francis, D. M.; Harari, P. M.; Chappell, R.; Tsuji, S.; Ritter, M. A. Increased Tumor Response to Neoadjuvant Therapy among Rectal Cancer Patients Taking Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers. Cancer 2016, 122 (16), 2487–2495. https://doi.org/10.1002/cncr.30079.

(91) Miller, J. C. Dietary Supplementation: A Retrospective Case Study. 2023.

(92) Pusceddu, S.; Vernieri, C.; Di Maio, M.; Marconcini, R.; Spada, F.; Massironi, S.; Ibrahim, T.; Brizzi, M. P.; Campana, D.; Faggiano, A.; Giuffrida, D.; Rinzivillo, M.; Cingarlini, S.; Aroldi, F.; Antonuzzo, L.; Berardi, R.; Catena, L.; De Divitiis, C.; Ermacora, P.; Perfetti, V.; Fontana, A.; Razzore, P.; Carnaghi, C.; Davì, M. V.; Cauchi, C.; Duro, M.; Ricci, S.; Fazio, N.; Cavalcoli, F.; Bongiovanni, A.; La Salvia, A.; Brighi, N.; Colao, A.; Puliafito, I.; Panzuto, F.; Ortolani, S.; Zaniboni, A.; Di Costanzo, F.; Torniai, M.; Bajetta, E.; Tafuto, S.; Garattini, S. K.; Femia, D.; Prinzi, N.; Concas, L.; Lo Russo, G.; Milione, M.; Giacomelli, L.; Buzzoni, R.; Delle Fave, G.; Mazzaferro, V.; de Braud, F. Metformin Use Is Associated With Longer Progression-Free Survival of Patients With Diabetes and Pancreatic Neuroendocrine Tumors Receiving Everolimus and/or Somatostatin Analogues. Gastroenterology 2018, 155 (2), 479-489.e7. https://doi.org/10.1053/j.gastro.2018.04.010.

(93) Trogdon, J. G.; Amin, K.; Gupta, P.; Urick, B. Y.; Reeder-Hayes, K. E.; Farley, J. F.; Wheeler, S. B.; Spees, L.; Lund, J. L. Providers’ Mediating Role for Medication Adherence among Cancer Survivors. PloS One 2021, 16 (11), e0260358. https://doi.org/10.1371/journal.pone.0260358.

(94) Dang, N.; Ren, Y. A Case of Superficial Kaposiform Hemangioendothelioma Treated with Oral Propranolol Combined with Topical Sirolimus. Vasc. Health Risk Manag. 2024, 20, 251–254. https://doi.org/10.2147/VHRM.S461505.

(95) Zhang, X.; Liao, H.; Zhu, X.; Shi, D.; Chen, X. A Successful Pregnancy in a Patient with Secondary Hypertension Caused by Adrenal Adenoma: A Case Report. BMC Pregnancy Childbirth 2019, 19 (1), 116. https://doi.org/10.1186/s12884-019-2262-2.

(96) Ma, Y.; Xia, Z.; Ye, C.; Lu, C.; Zhou, S.; Pan, J.; Liu, C.; Zhang, J.; Liu, T.; Hu, T.; Xie, L.; Wu, G.; Zhao, Y. AGTR1 Promotes Lymph Node Metastasis in Breast Cancer by Upregulating CXCR4/SDF-1α and Inducing Cell Migration and Invasion. Aging 2019, 11 (12), 3969–3992. https://doi.org/10.18632/aging.102032.

(97) Liang, Y.; Pu, R.; Huang, X.; Li, S.; Chen, Y.; Tang, W. Airway Obstruction as the Primary Manifestation of Infantile Thyroid Hemangioma. Ital. J. Pediatr. 2020, 46 (1), 157. https://doi.org/10.1186/s13052-020-00904-6.

(98) Dong, J.-Y.; Ning, J.-X.; Li, K.; Liu, C.; Wang, X.-X.; Li, R.-H.; Yue, L.-L.; Huang, Y.-Y.; Liu, S.-H. Analysis of Factors Affecting the Therapeutic Effect of Propranolol for Infantile Haemangioma of the Head and Neck. Sci. Rep. 2017, 7 (1), 342. https://doi.org/10.1038/s41598-017-00495-z.

(99) Hosoya, R.; Uesawa, Y.; Ishii-Nozawa, R.; Kagaya, H. Analysis of Factors Associated with Hiccups Based on the Japanese Adverse Drug Event Report Database. PloS One 2017, 12 (2), e0172057. https://doi.org/10.1371/journal.pone.0172057.

(100) Zhang, G.-H.; Miao, F.-A.; Xu, J.-G.; Zhang, Y. Angiotensin II Enhances the Proliferation of Natural Killer/T-Cell Lymphoma Cells via Activating PI3K/Akt Signaling Pathway. Biosci. Rep. 2020, 40 (10), BSR20202388. https://doi.org/10.1042/BSR20202388.

(101) Hicks, B. M.; Filion, K. B.; Yin, H.; Sakr, L.; Udell, J. A.; Azoulay, L. Angiotensin Converting Enzyme Inhibitors and Risk of Lung Cancer: Population Based Cohort Study. BMJ 2018, 363, k4209. https://doi.org/10.1136/bmj.k4209.

(102) Early, S.; Brown, A.; Xu, L.; Stankovic, K. M. Angiotensin-Receptor Blockers Prevent Vestibular Schwannoma-Associated Hearing Loss. Otol. Neurotol. Off. Publ. Am. Otol. Soc. Am. Neurotol. Soc. Eur. Acad. Otol. Neurotol. 2025, 46 (2), 183–189. https://doi.org/10.1097/MAO.0000000000004376.

(103) Huang, T.; Townsend, M. K.; Dood, R. L.; Sood, A. K.; Tworoger, S. S. Antihypertensive Medication Use and Ovarian Cancer Survival. Gynecol. Oncol. 2021, 163 (2), 342–347. https://doi.org/10.1016/j.ygyno.2021.09.009.

(104) Freites-Martinez, A.; Chan, D.; Sibaud, V.; Shapiro, J.; Fabbrocini, G.; Tosti, A.; Cho, J.; Goldfarb, S.; Modi, S.; Gajria, D.; Norton, L.; Paus, R.; Cigler, T.; Lacouture, M. E. Assessment of Quality of Life and Treatment Outcomes of Patients With Persistent Postchemotherapy Alopecia. JAMA Dermatol. 2019, 155 (6), 724–728. https://doi.org/10.1001/jamadermatol.2018.5071.

(105) Moon, S.; Lee, H.-Y.; Jang, J.; Park, S. K. Association Between Angiotensin II Receptor Blockers and the Risk of Lung Cancer Among Patients With Hypertension From the Korean National Health Insurance Service-National Health Screening Cohort. J. Prev. Med. Public Health Yebang Uihakhoe Chi 2020, 53 (6), 476–486. https://doi.org/10.3961/jpmph.20.405.

(106) Haap, M.; Blaschka, F.; Lehmann, R.; Hoyer, A.; Müssig, K. Association Between Urinary Catecholamine Excretion and Urine Volume. Horm. Metab. Res. Horm. Stoffwechselforschung Horm. Metab. 2019, 51 (8), 531–538. https://doi.org/10.1055/a-0926-3532.

(107) Hsu, C. D.; Hinton, S. P.; Reeder-Hayes, K. E.; Sanoff, H. K.; Lund, J. L. Association between Concomitant Use of Hydrochlorothiazide and Adverse Chemotherapy-Related Events among Older Women with Breast Cancer Treated with Cyclophosphamide. Cancer Epidemiol. Biomark. Prev. Publ. Am. Assoc. Cancer Res. Cosponsored Am. Soc. Prev. Oncol. 2020, 29 (2), 520–523. https://doi.org/10.1158/1055-9965.EPI-19-1079.

(108) Letellier, T.; Leborgne, F.; Kerleau, C.; Gaultier, A.; Dantal, J.; Ville, S.; Divat Consortium. Association between Use of Hydrochlorothiazide and Risk of Keratinocyte Cancers in Kidney Transplant Recipients. Clin. J. Am. Soc. Nephrol. CJASN 2020, 15 (12), 1804–1813. https://doi.org/10.2215/CJN.02560220.

(109) Pottegård, A.; Pedersen, S. A.; Schmidt, S. A. J.; Hölmich, L. R.; Friis, S.; Gaist, D. Association of Hydrochlorothiazide Use and Risk of Malignant Melanoma. JAMA Intern. Med. 2018, 178 (8), 1120–1122. https://doi.org/10.1001/jamainternmed.2018.1652.

(110) Yin, H.; Yang, M.; Sun, W.; Zhang, R.; Zhen, D.; Tang, X. Association of RAAS Inhibitors on Osteoporosis and Fracture Risk in the Hypertensive Population-A Prospective Population-Based Cohort Study in Lanzhou, China. BMC Musculoskelet. Disord. 2024, 25 (1), 797. https://doi.org/10.1186/s12891-024-07909-w.

(111) Balkrishnan, R.; Desai, R. P.; Narayan, A.; Camacho, F. T.; Flausino, L. E.; Chammas, R. Associations between Initiating Antihypertensive Regimens on Stage I-III Colorectal Cancer Outcomes: A Medicare SEER Cohort Analysis. Cancer Med. 2021, 10 (15), 5347–5357. https://doi.org/10.1002/cam4.4088.

(112) Wu, C.; Guo, L.; Wang, L.; Li, J.; Wang, C.; Song, D. Associations between Short-Term Efficacy and Clinical Characteristics of Infantile Hemangioma Treated by Propranolol. Medicine (Baltimore) 2019, 98 (6), e14346. https://doi.org/10.1097/MD.0000000000014346.

(113) Brasky, T. M.; Flores, K. F.; Larson, J. C.; Newton, A. M.; Shadyab, A. H.; Watanabe, J. H.; Lane, D. S.; Thomson, C. A.; LaCroix, A. Z. Associations of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use with Colorectal Cancer Risk in the Women’s Health Initiative. Cancer Epidemiol. Biomark. Prev. Publ. Am. Assoc. Cancer Res. Cosponsored Am. Soc. Prev. Oncol. 2021, 30 (5), 1029–1032. https://doi.org/10.1158/1055-9965.EPI-20-1401.

(114) Özdemir, Z. C.; Düzenli Kar, Y.; Şöhret, N. C.; Kebapçı, M.; Bör, Ö. Beta Blocker and Steroid Therapy in the Treatment of Infantile Hepatic Hemangioendothelioma. Drug Discov. Ther. 2017, 11 (3), 161–164. https://doi.org/10.5582/ddt.2017.01025.

(115) Udumyan, R.; Montgomery, S.; Duberg, A.-S.; Fang, F.; Valdimarsdottir, U.; Ekbom, A.; Smedby, K. E.; Fall, K. Beta-Adrenergic Receptor Blockers and Liver Cancer Mortality in a National Cohort of Hepatocellular Carcinoma Patients. Scand. J. Gastroenterol. 2020, 55 (5), 597–605. https://doi.org/10.1080/00365521.2020.1762919.

(116) Jung, M.; Li, S.; Deng, Z.; Li, J.; Li, M.; Basran, S.; Langston, M. E.; Chung, B. I. Calcium Channel Blocker Versus Renin-Angiotensin System Inhibitor in Risk of Kidney Cancer Among Patients With Hypertension: A Propensity Score-Matched Cohort Study. Cancer Med. 2024, 13 (22), e70429. https://doi.org/10.1002/cam4.70429.

(117) Main, A. M.; Benndorf, G.; Feldt-Rasmussen, U.; Fugleholm, K.; Kistorp, T.; Loya, A. C.; Poulsgaard, L.; Rasmussen, Å. K.; Rossing, M.; Sølling, C.; Klose, M. C. Case Report: Giant Paraganglioma of the Skull Base With Two Somatic Mutations in SDHB and PTEN Genes. Front. Endocrinol. 2022, 13, 857504. https://doi.org/10.3389/fendo.2022.857504.

(118) Qiu, Z.; Ke, F.; Zhu, X. Case Report: Alectinib-Associated Intestinal Ulceration and Colitis in a Patient with Non-Small Cell Lung Cancer and Effective Treatment with Mesalazine. Pathol. Oncol. Res. POR 2025, 31, 1612040. https://doi.org/10.3389/pore.2025.1612040.

(119) Tani, S.; Kunimoto, K.; Inaba, Y.; Mikita, N.; Kaminaka, C.; Kanazawa, N.; Yamamoto, Y.; Kakimoto, N.; Suenaga, T.; Takeuchi, T.; Suzuki, H.; Jinnin, M. Change of Serum Cytokine Profiles by Propranolol Treatment in Patients with Infantile Hemangioma. Drug Discov. Ther. 2020, 14 (2), 89–92. https://doi.org/10.5582/ddt.2020.03014.

(120) Fernández Faith, E.; Shah, S.; Witman, P. M.; Harfmann, K.; Bradley, F.; Blei, F.; Pope, E.; Alsumait, A.; Gupta, D.; Covelli, I.; Streicher, J. L.; Cotton, C.; Tollefson, M.; Nguyen, H.; Hunt, R.; Moore-Clingenpeel, M.; Frieden, I. J. Clinical Features, Prognostic Factors, and Treatment Interventions for Ulceration in Patients With Infantile Hemangioma. JAMA Dermatol. 2021, 157 (5), 566–572. https://doi.org/10.1001/jamadermatol.2021.0469.

(121) Wan, W.; Nguyen, B.; Graybill, S.; Kim, J. Clonidine Suppression Testing for Pheochromocytoma in Neurofibromatosis Type 1. BMJ Case Rep. 2019, 12 (6), e228263. https://doi.org/10.1136/bcr-2018-228263.

(122) Gokhale, M.; Girman, C.; Chen, Y.; Pate, V.; Funk, M. J.; Stürmer, T. Comparison of Diagnostic Evaluations for Cough among Initiators of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers. Pharmacoepidemiol. Drug Saf. 2016, 25 (5), 512–520. https://doi.org/10.1002/pds.3977.

(123) Xue, C.; Zhou, C.; Yang, B.; Lv, J.; Dai, B.; Yu, S.; Wang, Y.; Zhao, G.; Mei, C. Comparison of Efficacy and Safety between Benidipine and Hydrochlorothiazide in Fosinopril-Treated Hypertensive Patients with Chronic Kidney Disease: Protocol for a Randomised Controlled Trial. BMJ Open 2017, 7 (2), e013672. https://doi.org/10.1136/bmjopen-2016-013672.

(124) Chen, S.; Liu, H.; Luo, P.; Yu, Y. Computed Tomography Combined with Confirmatory Tests for the Diagnosis of Aldosterone-Producing Adenoma. Endocr. J. 2021, 68 (3), 299–306. https://doi.org/10.1507/endocrj.EJ20-0395.

(125) Sio, T. T.; Atherton, P. J.; Pederson, L. D.; Zhen, W. K.; Mutter, R. W.; Garces, Y. I.; Ma, D. J.; Leenstra, J. L.; Rwigema, J.-C. M.; Dakhil, S.; Bearden, J. D.; van der Veen, S. J.; Ganti, A. K.; Schild, S. E.; Miller, R. C. Daily Lisinopril vs Placebo for Prevention of Chemoradiation-Induced Pulmonary Distress in Patients With Lung Cancer (Alliance MC1221): A Pilot Double-Blind Randomized Trial. Int. J. Radiat. Oncol. Biol. Phys. 2019, 103 (3), 686–696. https://doi.org/10.1016/j.ijrobp.2018.10.035.

(126) Hagberg, K. W.; Sahasrabuddhe, V. V.; McGlynn, K. A.; Jick, S. S. Does Angiotensin-Converting Enzyme Inhibitor and β-Blocker Use Reduce the Risk of Primary Liver Cancer? A Case-Control Study Using the U.K. Clinical Practice Research Datalink. Pharmacotherapy 2016, 36 (2), 187–195. https://doi.org/10.1002/phar.1704.

(127) Giachetti, A.; Díaz, M. S.; Boggio, P.; Posadas Martínez, M. L. Early Propranolol Treatment of Infantile Hemangiomas Improves Outcome. An. Bras. Dermatol. 2023, 98 (3), 310–315. https://doi.org/10.1016/j.abd.2022.04.008.

(128) Bejjanki, K. M.; Akhtar, K.; Gupta, A. P.; Kaliki, S. Effect of Oral Propranolol on Periocular Infantile Capillary Hemangioma: Outcomes Based on Extent of Involvement. Middle East Afr. J. Ophthalmol. 2021, 28 (1), 6–10. https://doi.org/10.4103/meajo.MEAJO_228_19.

(129) Brady, S. L.; Wong, K. K.; Doubrovin, M.; Han, Y.; Li, Y.; Wu, S.; Hossain, A. K. M. M.; Chism, C. B.; Naik, M. H.; Rossi, M.; Shulkin, B. L. Effect of Propranolol on 18F-Fluorodeoxyglucose Uptake in Brown Adipose Tissue in Children and Young Adults with Neoplastic Diseases. Mol. Imaging Biol. 2021, 23 (2), 260–269. https://doi.org/10.1007/s11307-020-01547-z.

(130) Kjølhede, P.; Bergdahl, O.; Borendal Wodlin, N.; Nilsson, L. Effect of Intrathecal Morphine and Epidural Analgesia on Postoperative Recovery after Abdominal Surgery for Gynecologic Malignancy: An Open-Label Randomised Trial. BMJ Open 2019, 9 (3), e024484. https://doi.org/10.1136/bmjopen-2018-024484.

(131) Pasquier, E.; André, N.; Street, J.; Chougule, A.; Rekhi, B.; Ghosh, J.; Philip, D. S. J.; Meurer, M.; MacKenzie, K. L.; Kavallaris, M.; Banavali, S. D. Effective Management of Advanced Angiosarcoma by the Synergistic Combination of Propranolol and Vinblastine-Based Metronomic Chemotherapy: A Bench to Bedside Study. EBioMedicine 2016, 6, 87–95. https://doi.org/10.1016/j.ebiom.2016.02.026.

(132) Anger, J.; Oliveira, E. M. de; Gabel, J. EFFECTIVENESS OF FIXED DOSES OF PROPRANOLOL IN THE TREATMENT OF HEMANGIOMAS REGARDLESS OF CHILD’S WEIGHT GAIN: A CASE REPORT. Rev. Paul. Pediatr. Orgao Of. Soc. Pediatr. Sao Paulo 2019, 37 (3), 392–395. https://doi.org/10.1590/1984-0462/;2019;37;3;00004.

(133) Muñoz-Garza, F. Z.; Ríos, M.; Roé-Crespo, E.; Bernabeu-Wittel, J.; Montserrat-García, M. T.; Puig, L.; Gich, I.; Baselga, E. Efficacy and Safety of Topical Timolol for the Treatment of Infantile Hemangioma in the Early Proliferative Stage: A Randomized Clinical Trial. JAMA Dermatol. 2021, 157 (5), 583–587. https://doi.org/10.1001/jamadermatol.2021.0596.

(134) Cho, E. J.; Kim, M. H.; Kim, Y.-H.; Chang, K.; Choi, D.-J.; Kang, W. C.; Shin, J.; Kim, S. H.; Lee, N.; Son, J. W.; Doh, J.-H.; Kim, W.-S.; Hong, S. J.; Rhee, M.-Y.; Ahn, Y.; Lim, S.-W.; Hong, S. P.; Choi, S.-Y.; Hyon, M. S.; Hwang, J.-Y.; Kwon, K.; Cha, K. S.; Ihm, S.-H.; Lee, J.-H.; Yoo, B.-S.; Kim, H.-S. Efficacy and Safety of Standard Dose Triple Combination of Telmisartan 80 Mg/Amlodipine 5 Mg/Chlorthalidone 25 Mg in Primary Hypertension: A Randomized, Double-Blind, Active-Controlled, Multicenter Phase 3 Trial. J. Clin. Hypertens. Greenwich Conn 2023, 25 (9), 817–827. https://doi.org/10.1111/jch.14707.

(135) Gill, D.; Gaston, D.; Bailey, E.; Hahn, A.; Gupta, S.; Batten, J.; Alex, A.; Boucher, K.; Stenehjem, D.; Agarwal, N. Efficacy of Eplerenone in the Management of Mineralocorticoid Excess in Men With Metastatic Castration-Resistant Prostate Cancer Treated With Abiraterone Without Prednisone. Clin. Genitourin. Cancer 2017, 15 (4), e599–e602. https://doi.org/10.1016/j.clgc.2016.12.008.

(136) Tsai, M.-C.; Liu, H.-C.; Yeung, C.-Y. Efficacy of Infantile Hepatic Hemangioma with Propranolol Treatment: A Case Report. Medicine (Baltimore) 2019, 98 (4), e14078. https://doi.org/10.1097/MD.0000000000014078.

(137) Ramaswamy, A.; Bhargava, P.; Gota, V.; Srinivas, S.; Sultana, N.; Mandavkar, S.; Jadhav, P.; Gandhi, K.; Mer, N.; Khan, N.; Vora, M.; Gujarathi, H.; Bhandare, M.; Chaudhari, V.; Shrikhande, S. V.; Ostwal, V. Efficacy of Losartan plus Modified FOLFIRINOX versus Modified FOLFIRINOX in Advanced Pancreatic Cancers: A Randomized Clinical Trial (AFPAC Study). Cancer 2025, 131 (13), e35945. https://doi.org/10.1002/cncr.35945.

(138) Li, Y.; Du, L.; Zhang, S.; Liu, C.; Ma, C.; Liu, X.; Xu, H.; Fan, Z.; Hu, S.; Wang, J.; Shao, L.; Peng, L.; Xiang, H.; Liang, X.; Zhang, W.; Zhao, H.; He, P.; Xu, J.; Li, Q.; Yang, L.; Wu, Y.; Zhang, L.; Fang, D.; Ye, H.; Zhang, L.; Zhang, L.; Zhang, X.; Wei, Z.; Peng, Y.; Pan, Q.; Li, Q.; Xu, J.; Xia, D.; Lv, Y.; Zhang, Z.; Yan, C.; Wang, J.; Wan, Y.; Xie, B.; Fang, H.; Yang, W.; Yan, W.; Chen, Y.; Zhang, S.; Zhang, X.; Rao, W.; Xia, X.; Qiao, Q.; Yu, R.; Ren, C.; Song, Y.; Yang, Y.; Li, J.; Wang, L.; Zhai, Z.; Liu, X.; Lu, X.; Li, M.; Jia, Y.; Wang, R.; Wang, D.; Cardenas, A.; Jin, Z.; Qi, X. Endoscopic Variceal Ligation Combined with Carvedilol versus Endoscopic Variceal Ligation Combined with Propranolol for the Treatment of Oesophageal Variceal Bleeding in Cirrhosis: Study Protocol for a Multicentre, Randomised Controlled Trial. BMJ Open 2025, 15 (4), e093866. https://doi.org/10.1136/bmjopen-2024-093866.

(139) Kidoguchi, S.; Sugano, N.; Kawauchi, R.; Nakashima, D.; Hayashi-Ishikawa, N.; Tokudome, G.; Yokoo, T. Evaluation of Various Confirmatory Tests for the Diagnosis of Aldosterone-Producing Adenoma. J. Renin-Angiotensin-Aldosterone Syst. JRAAS 2020, 21 (2), 1470320320919610. https://doi.org/10.1177/1470320320919610.

(140) Emery, I. F.; Gopalan, A.; Wood, S.; Chow, K.-H.; Battelli, C.; George, J.; Blaszyk, H.; Florman, J.; Yun, K. Expression and Function of ABCG2 and XIAP in Glioblastomas. J. Neurooncol. 2017, 133 (1), 47–57. https://doi.org/10.1007/s11060-017-2422-z.

(141) Wada, F.; Koga, H.; Akiba, J.; Niizeki, T.; Iwamoto, H.; Ikezono, Y.; Nakamura, T.; Abe, M.; Masuda, A.; Sakaue, T.; Tanaka, T.; Kakuma, T.; Yano, H.; Torimura, T. High Expression of CD44v9 and xCT in Chemoresistant Hepatocellular Carcinoma: Potential Targets by Sulfasalazine. Cancer Sci. 2018, 109 (9), 2801–2810. https://doi.org/10.1111/cas.13728.

(142) Ohara, N.; Uemura, Y.; Mezaki, N.; Kimura, K.; Kaneko, M.; Kuwano, H.; Ebe, K.; Fujita, T.; Komeyama, T.; Usuda, H.; Yamazaki, Y.; Maekawa, T.; Sasano, H.; Kaneko, K.; Kamoi, K. Histopathological Analysis of Spontaneous Large Necrosis of Adrenal Pheochromocytoma Manifested as Acute Attacks of Alternating Hypertension and Hypotension: A Case Report. J. Med. Case Reports 2016, 10 (1), 279. https://doi.org/10.1186/s13256-016-1068-3.

(143) Jiao-Ling, L.; Xiu-Ping, G.; Kun-Shan, C.; Qiu-Ming, H.; Xiao-Fen, L.; Bo-Yang, Y.; Qian, F. Huge Fetal Hepatic Hemangioma: Prenatal Diagnosis on Ultrasound and Prognosis. BMC Pregnancy Childbirth 2018, 18 (1), 2. https://doi.org/10.1186/s12884-017-1635-7.

(144) Pedersen, S. A.; Gaist, D.; Schmidt, S. A. J.; Hölmich, L. R.; Friis, S.; Pottegård, A. Hydrochlorothiazide Use and Risk of Nonmelanoma Skin Cancer: A Nationwide Case-Control Study from Denmark. J. Am. Acad. Dermatol. 2018, 78 (4), 673-681.e9. https://doi.org/10.1016/j.jaad.2017.11.042.

(145) Pottegård, A.; Hallas, J.; Olesen, M.; Svendsen, M. T.; Habel, L. A.; Friedman, G. D.; Friis, S. Hydrochlorothiazide Use Is Strongly Associated with Risk of Lip Cancer. J. Intern. Med. 2017, 282 (4), 322–331. https://doi.org/10.1111/joim.12629.

(146) Huang, T.; Poole, E. M.; Eliassen, A. H.; Okereke, O. I.; Kubzansky, L. D.; Sood, A. K.; Forman, J. P.; Tworoger, S. S. Hypertension, Use of Antihypertensive Medications, and Risk of Epithelial Ovarian Cancer. Int. J. Cancer 2016, 139 (2), 291–299. https://doi.org/10.1002/ijc.30066.

(147) Miao, L.; Chen, W.; Zhou, L.; Wan, H.; Gao, B.; Feng, Y. Impact of Angiotensin I-Converting Enzyme Inhibitors and Angiotensin II Type-1 Receptor Blockers on Survival of Patients with NSCLC. Sci. Rep. 2016, 6, 21359. https://doi.org/10.1038/srep21359.

(148) Cho, M. A.; Jeong, S. Y.; Sohn, I.; Kim, M.-S.; Kang, J. H.; Paik, E. S.; Lee, Y.-Y.; Choi, C. H. Impact of Angiotensin Receptor Blockers, Beta Blockers, Calcium Channel Blockers and Thiazide Diuretics on Survival of Ovarian Cancer Patients. Cancer Res. Treat. 2020, 52 (2), 645–654. https://doi.org/10.4143/crt.2019.509.

(149) Sever, N.; Yunusov, E.; Çelebi, A.; Yaşar, A.; Majidova, N.; Kocaaslan, E.; Erel, P.; Ağyol, Y.; Güren, A. K.; Işık, S.; Arıkan, R.; Ercelep, Ö.; Köstek, O.; Bayoğlu, İ. V.; Sarıc, M. Impact of Renin Angiotensin System Inhibitors on Survival of Patients with Metastatic Non-Small Cell Lung Cancer. Ann. Saudi Med. 2025, 45 (1), 18–24. https://doi.org/10.5144/0256-4947.2025.18.

(150) Prasad, A.; Sinha, A. K.; Kumar, B.; Prasad, A.; Kumari, M. Individualized Dosing of Oral Propranolol for Treatment of Infantile Hemangioma: A Prospective Study. Pan Afr. Med. J. 2019, 32, 155. https://doi.org/10.11604/pamj.2019.32.155.16760.

(151) Baniya, R.; Chaudhary, A.; Poudel Upadhyaya, A.; Rijal, P. Infantile Subglottic Hemangioma: A Case ReportInfantile Subglottic Hemangioma: A Case Report. JNMA J. Nepal Med. Assoc. 2024, 62 (271), 211–213. https://doi.org/10.31729/jnma.8500.

(152) Mariani, L. G.; Ferreira, L. M.; Rovaris, D. L.; Bonamigo, R. R.; Kiszewski, A. E. Infantile Hemangiomas: Risk Factors for Complications, Recurrence and Unaesthetic Sequelae. An. Bras. Dermatol. 2022, 97 (1), 37–44. https://doi.org/10.1016/j.abd.2021.05.009.

(153) Choy, C.; Raytis, J. L.; Smith, D. D.; Duenas, M.; Neman, J.; Jandial, R.; Lew, M. W. Inhibition of Β2-Adrenergic Receptor Reduces Triple-Negative Breast Cancer Brain Metastases: The Potential Benefit of Perioperative β-Blockade. Oncol. Rep. 2016, 35 (6), 3135–3142. https://doi.org/10.3892/or.2016.4710.

(154) Franchi, M.; Torrigiani, G.; Kjeldsen, S. E.; Mancia, G.; Corrao, G. Long-Term Exposure to Antihypertensive Drugs and the Risk of Cancer Occurrence: Evidence from a Large Population-Based Study. J. Hypertens. 2024, 42 (12), 2107–2114. https://doi.org/10.1097/HJH.0000000000003841.

(155) Hermans, M. M.; Rietman, A. B.; Schappin, R.; de Laat, P. C. J.; Mendels, E. J.; Breur, J. M. P. J.; Langeveld, H. R.; de Wildt, S. N.; Breugem, C. C.; de Graaf, M.; Raphael, M. F.; Pasmans, S. G. M. A. Long-Term Neurocognitive Functioning of Children Treated with Propranolol or Atenolol for Infantile Hemangioma. Eur. J. Pediatr. 2023, 182 (2), 757–767. https://doi.org/10.1007/s00431-022-04674-7.

(156) Lovin, B. D.; Nader, M.-E.; Qing, Y.; Hernandez, M.; Raza, S.; DeMonte, F.; Gidley, P. W. Losartan May Not Prevent Vestibular Schwannoma Growth or Related Hearing Loss During Observation. Otol. Neurotol. Off. Publ. Am. Otol. Soc. Am. Neurotol. Soc. Eur. Acad. Otol. Neurotol. 2024, 45 (6), 690–695. https://doi.org/10.1097/MAO.0000000000004214.

(157) Matsumoto, K.; Shiroyama, T.; Miyake, K.; Yamamoto, Y.; Kuge, T.; Yoneda, M.; Yamamoto, M.; Naito, Y.; Suga, Y.; Fukushima, K.; Koyama, S.; Iwahori, K.; Hirata, H.; Nagatomo, I.; Takeda, Y.; Kumanogoh, A. Management of Severe Hypertension Due to Lenvatinib in Patients with Advanced Thymic Carcinoma: A Case Report. Medicine (Baltimore) 2022, 101 (1), e28476. https://doi.org/10.1097/MD.0000000000028476.

(158) Zhu, Z.; Cai, P.; Zhu, J.; Chen, J.; Wu, B.; Gu, Z.; Huang, S.; Wang, J. Neonatal Giant Hepatic Hemangioma: A Case Report. Medicine (Baltimore) 2018, 97 (42), e12863. https://doi.org/10.1097/MD.0000000000012863.

(159) Ge, J.; Zheng, J.; Zhang, L.; Yuan, W.; Zhao, H. Oral Propranolol Combined with Topical Timolol for Compound Infantile Hemangiomas: A Retrospective Study. Sci. Rep. 2016, 6, 19765. https://doi.org/10.1038/srep19765.

(160) Tan, J. M. C.; Lim, H. W.; Koh, M. J.-A. Oral Propranolol for the Treatment of Infantile Haemangiomas in Singapore. Singapore Med. J. 2021, 62 (3), 139–142. https://doi.org/10.11622/smedj.2020008.

(161) Zaaroura, H.; Tibi, A.; Avitan-Hersh, E.; Khamaysi, Z. Our Experience in Treating Infantile Hemangioma: Prognostic Factors for Relapse After Propranolol Discontinuation. Adv. Ther. 2025, 42 (1), 537–547. https://doi.org/10.1007/s12325-024-03017-2.

(162) Gandhi, S.; Pandey, M. R.; Attwood, K.; Ji, W.; Witkiewicz, A. K.; Knudsen, E. S.; Allen, C.; Tario, J. D.; Wallace, P. K.; Cedeno, C. D.; Levis, M.; Stack, S.; Funchain, P.; Drabick, J. J.; Bucsek, M. J.; Puzanov, I.; Mohammadpour, H.; Repasky, E. A.; Ernstoff, M. S. Phase I Clinical Trial of Combination Propranolol and Pembrolizumab in Locally Advanced and Metastatic Melanoma: Safety, Tolerability, and Preliminary Evidence of Antitumor Activity. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2021, 27 (1), 87–95. https://doi.org/10.1158/1078-0432.CCR-20-2381.

(163) Everatt, R.; Kuzmickienė, I.; Brasiūnienė, B.; Vincerževskienė, I.; Intaitė, B.; Cicėnas, S.; Lisauskienė, I. Postdiagnostic Use of Antihypertensive Medications and Survival in Colorectal, Lung, Corpus Uteri, Melanoma and Kidney Cancer Patients with Hypertension. BMC Cancer 2025, 25 (1), 38. https://doi.org/10.1186/s12885-024-13273-8.

(164) Chen, Q.; Chang, S.-J.; Gao, W.; Chang, L.; Qiu, Y.; Lin, X. Practical Surgical Technique Using the SMISS Approach for Lip Reduction in Involuted Lip Infantile Hemangiomas. BMC Pediatr. 2024, 24 (1), 368. https://doi.org/10.1186/s12887-024-04838-4.

(165) Anwar, T.; Malm-Buatsi, E. Propranolol as an Effective Therapy for Infantile Haemangioma of the Urinary Bladder. BMJ Case Rep. 2019, 12 (2), e226929. https://doi.org/10.1136/bcr-2018-226929.

(166) De Giorgi, V.; Grazzini, M.; Benemei, S.; Marchionni, N.; Botteri, E.; Pennacchioli, E.; Geppetti, P.; Gandini, S. Propranolol for Off-Label Treatment of Patients With Melanoma: Results From a Cohort Study. JAMA Oncol. 2018, 4 (2), e172908. https://doi.org/10.1001/jamaoncol.2017.2908.

(167) Zhou, C.; Chen, X.; Zeng, W.; Peng, C.; Huang, G.; Li, X.; Ouyang, Z.; Luo, Y.; Xu, X.; Xu, B.; Wang, W.; He, R.; Zhang, X.; Zhang, L.; Liu, J.; Knepper, T. C.; He, Y.; McLeod, H. L. Propranolol Induced G0/G1/S Phase Arrest and Apoptosis in Melanoma Cells via AKT/MAPK Pathway. Oncotarget 2016, 7 (42), 68314–68327. https://doi.org/10.18632/oncotarget.11599.

(168) Stringari, G.; Barbato, G.; Zanzucchi, M.; Marchesi, M.; Cerasoli, G.; Tchana, B.; Gritti, A.; Boccaletti, V.; Lombardi, A. A.; Carano, N. Propranolol Treatment for Infantile Hemangioma: A Case Series of Sixty-Two Patients. Pediatr. Medica E Chir. Med. Surg. Pediatr. 2016, 38 (2), 113. https://doi.org/10.4081/pmc.2016.113.

(169) Ramondetta, L. M.; Hu, W.; Thaker, P. H.; Urbauer, D. L.; Chisholm, G. B.; Westin, S. N.; Sun, Y.; Ramirez, P. T.; Fleming, N.; Sahai, S. K.; Nick, A. M.; Arevalo, J. M. G.; Dizon, T.; Coleman, R. L.; Cole, S. W.; Sood, A. K. Prospective Pilot Trial with Combination of Propranolol with Chemotherapy in Patients with Epithelial Ovarian Cancer and Evaluation on Circulating Immune Cell Gene Expression. Gynecol. Oncol. 2019, 154 (3), 524–530. https://doi.org/10.1016/j.ygyno.2019.07.004.

(170) Gipsman, A. I.; Treat, J. R.; Piccione, J. Rare Airway Tumor in a Previously Healthy Adolescent Successfully Treated with Endoscopic Resection and Oral Propranolol. Pediatr. Pulmonol. 2023, 58 (7), 2142–2144. https://doi.org/10.1002/ppul.26421.

(171) Baruch, S.; Ben Amitai, D.; Friedland, R. Rebound Growth of Infantile Hemangiomas after Propranolol versus Atenolol Treatment: A Retrospective Study. Dermatol. Basel Switz. 2024, 240 (5–6), 879–884. https://doi.org/10.1159/000542001.

(172) Chiu, H.-F.; Huang, Y.-C.; Lu, Y.-Y.; Han, Y.-C.; Shen, Y.-C.; Golovinskaia, O.; Venkatakrishnan, K.; Wang, C.-K. Regulatory/Modulatory Effect of Prune Essence Concentrate on Intestinal Function and Blood Lipids. Pharm. Biol. 2017, 55 (1), 974–979. https://doi.org/10.1080/13880209.2017.1285323.

(173) Htoo, P. T.; Stürmer, T.; Jonsson-Funk, M.; Pate, V.; Simpson, R. J.; Lund, J. L. Renin-Angiotensin-Aldosterone System-Based Antihypertensive Agents and the Risk of Colorectal Cancer Among Medicare Beneficiaries. Epidemiol. Camb. Mass 2019, 30 (6), 867–875. https://doi.org/10.1097/EDE.0000000000001065.

(174) Zhu, X.-X.; Li, J.-H.; Fang, P.; Qu, X.-F.; Liang, L.-J.; Lai, J.-M.; Yin, X.-Y. Renin-Angiotensin System Inhibitors Improve the Survival of Cholangiocarcinoma: A Propensity Score-Matched Cohort Study. BMC Cancer 2023, 23 (1), 826. https://doi.org/10.1186/s12885-023-11152-2.

(175) Jones, M. R.; Schrader, K. A.; Shen, Y.; Pleasance, E.; Ch’ng, C.; Dar, N.; Yip, S.; Renouf, D. J.; Schein, J. E.; Mungall, A. J.; Zhao, Y.; Moore, R.; Ma, Y.; Sheffield, B. S.; Ng, T.; Jones, S. J. M.; Marra, M. A.; Laskin, J.; Lim, H. J. Response to Angiotensin Blockade with Irbesartan in a Patient with Metastatic Colorectal Cancer. Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. 2016, 27 (5), 801–806. https://doi.org/10.1093/annonc/mdw060.

(176) Sharma, A. K.; Rastogi, S.; Goyal, R. K. Retrospective Analysis of Neoplasms in Patients Using Angiotensin Receptor Blockers. Sci. Rep. 2024, 14 (1), 15774. https://doi.org/10.1038/s41598-024-64867-y.

(177) Eworuke, E.; Haug, N.; Bradley, M.; Cosgrove, A.; Zhang, T.; Dee, E. C.; Adimadhyam, S.; Petrone, A.; Lee, H.; Woodworth, T.; Toh, S. Risk of Nonmelanoma Skin Cancer in Association With Use of Hydrochlorothiazide-Containing Products in the United States. JNCI Cancer Spectr. 2021, 5 (2), pkab009. https://doi.org/10.1093/jncics/pkab009.

(178) Daniels, B.; Pearson, S.-A.; Vajdic, C. M.; Pottegård, A.; Buckley, N. A.; Zoega, H. Risk of Squamous Cell Carcinoma of the Lip and Cutaneous Melanoma in Older Australians Using Hydrochlorothiazide: A Population-Based Case-Control Study. Basic Clin. Pharmacol. Toxicol. 2020, 127 (4), 320–328.

(179) El Hachem, M.; Gesualdo, F.; Diociaiuti, A.; Berti, I.; Vercellino, N.; Boccaletti, V.; Neri, I.; Porcedda, G.; Greco, A.; Carnevale, C.; Oranges, T.; Cutrone, M.; Dalmonte, P. Safety and Effectiveness of Oral Propranolol for Infantile Hemangiomas Started before 5 Weeks and after 5 Months of Age: An Italian Multicenter Experience. Ital. J. Pediatr. 2017, 43 (1), 40. https://doi.org/10.1186/s13052-017-0357-9.

(180) Costa, M. C.; Andrade, O. G. C. de; Pereira, L. de C.; Costa, I. M. C. Success in the Use of Oral Propranolol in the Treatment of Infantile Hemangioma in Nasal Tip - Report of Two Cases. An. Bras. Dermatol. 2020, 95 (2), 207–209. https://doi.org/10.1016/j.abd.2019.05.005.

(181) Jeon, S.-Y.; Lee, N.-R.; Yim, C.-Y. Successful Re-Administration of Pazopanib in a Patient with Metastatic Renal Cell Carcinoma and a History of Pazopanib-Induced Nephrotic Syndrome: A Case Report. BMC Nephrol. 2019, 20 (1), 1. https://doi.org/10.1186/s12882-018-1181-1.

(182) O’Bryhim, B. E.; Li, A. S.; Bayliss, S. J.; Tychsen, L.; Lueder, G. T.; Rajagopal, R. Successful Treatment of an Exudative Choroidal Hemangioma with Oral Propranolol in a 10-Year-Old Boy. J. AAPOS Off. Publ. Am. Assoc. Pediatr. Ophthalmol. Strabismus 2019, 23 (4), 236–238. https://doi.org/10.1016/j.jaapos.2019.02.004.

(183) Baker, F. L.; Bigley, A. B.; Agha, N. H.; Pedlar, C. R.; O’Connor, D. P.; Bond, R. A.; Bollard, C. M.; Katsanis, E.; Simpson, R. J. Systemic β-Adrenergic Receptor Activation Augments the Ex Vivo Expansion and Anti-Tumor Activity of Vγ9Vδ2 T-Cells. Front. Immunol. 2019, 10, 3082. https://doi.org/10.3389/fimmu.2019.03082.

(184) Castaneda, S.; Melendez-Lopez, S.; Garcia, E.; De la Cruz, H.; Sanchez-Palacio, J. The Role of the Pharmacist in the Treatment of Patients with Infantile Hemangioma Using Propranolol. Adv. Ther. 2016, 33 (10), 1831–1839. https://doi.org/10.1007/s12325-016-0391-9.

(185) Gómez-Acebo, I.; Dierssen-Sotos, T.; Palazuelos, C.; Pérez-Gómez, B.; Lope, V.; Tusquets, I.; Alonso, M. H.; Moreno, V.; Amiano, P.; Molina de la Torre, A. J.; Barricarte, A.; Tardon, A.; Camacho, A.; Peiro-Perez, R.; Marcos-Gragera, R.; Muñoz, M.; Michelena-Echeveste, M. J.; Ortega Valin, L.; Guevara, M.; Castaño-Vinyals, G.; Aragonés, N.; Kogevinas, M.; Pollán, M.; Llorca, J. The Use of Antihypertensive Medication and the Risk of Breast Cancer in a Case-Control Study in a Spanish Population: The MCC-Spain Study. PloS One 2016, 11 (8), e0159672. https://doi.org/10.1371/journal.pone.0159672.

(186) De Giorgi, V.; Grazzini, M.; Benemei, S.; Marchionni, N.; Botteri, E.; Pennacchioli, E.; Geppetti, P.; Gandini, S. Propranolol for Off-Label Treatment of Patients with Melanoma: Results from a Cohort Study. JAMA Oncol. 2018, 4 (2), e172908–e172908.

(187) Tascilar, K.; Azoulay, L.; Dell’Aniello, S.; Bartels, D. B.; Suissa, S. The Use of Telmisartan and the Incidence of Cancer. Am. J. Hypertens. 2016, 29 (12), 1358–1365. https://doi.org/10.1093/ajh/hpw095.

(188) Chang, P.-Y.; Chung, C.-H.; Chang, W.-C.; Lin, C.-S.; Lin, H.-H.; Dai, M.-S.; Ho, C.-L.; Chien, W.-C. The Effect of Propranolol on the Prognosis of Hepatocellular Carcinoma: A Nationwide Population-Based Study. PloS One 2019, 14 (5), e0216828. https://doi.org/10.1371/journal.pone.0216828.

(189) Mandilaras, V.; Bouganim, N.; Yin, H.; Asselah, J.; Azoulay, L. The Use of Drugs Acting on the Renin-Angiotensin System and the Incidence of Pancreatic Cancer. Br. J. Cancer 2017, 116 (1), 103–108. https://doi.org/10.1038/bjc.2016.375.

(190) Holdhoff, M.; Ye, X.; Supko, J. G.; Nabors, L. B.; Desai, A. S.; Walbert, T.; Lesser, G. J.; Read, W. L.; Lieberman, F. S.; Lodge, M. A.; Leal, J.; Fisher, J. D.; Desideri, S.; Grossman, S. A.; Wahl, R. L.; Schiff, D. Timed Sequential Therapy of the Selective T-Type Calcium Channel Blocker Mibefradil and Temozolomide in Patients with Recurrent High-Grade Gliomas. Neuro-Oncol. 2017, 19 (6), 845–852. https://doi.org/10.1093/neuonc/nox020.

(191) Mehta, A.; Bajaj, M. S.; Pushker, N.; Chawla, B.; Pujari, A.; Grewal, S. S.; Grewal, S. P. S.; Singh, S. R.; Kishore, A.; Yadav, N. S. To Compare Intralesional and Oral Propranolol for Treating Periorbital and Eyelid Capillary Hemangiomas. Indian J. Ophthalmol. 2019, 67 (12), 1974–1980. https://doi.org/10.4103/ijo.IJO_59_19.

(192) Murphy, J. E.; Wo, J. Y.; Ryan, D. P.; Clark, J. W.; Jiang, W.; Yeap, B. Y.; Drapek, L. C.; Ly, L.; Baglini, C. V.; Blaszkowsky, L. S.; Ferrone, C. R.; Parikh, A. R.; Weekes, C. D.; Nipp, R. D.; Kwak, E. L.; Allen, J. N.; Corcoran, R. B.; Ting, D. T.; Faris, J. E.; Zhu, A. X.; Goyal, L.; Berger, D. L.; Qadan, M.; Lillemoe, K. D.; Talele, N.; Jain, R. K.; DeLaney, T. F.; Duda, D. G.; Boucher, Y.; Fernández-Del Castillo, C.; Hong, T. S. Total Neoadjuvant Therapy With FOLFIRINOX in Combination With Losartan Followed by Chemoradiotherapy for Locally Advanced Pancreatic Cancer: A Phase 2 Clinical Trial. JAMA Oncol. 2019, 5 (7), 1020–1027. https://doi.org/10.1001/jamaoncol.2019.0892.

(193) Liu, Z.; Yeo, Y. H.; Jackson, C.; Trimble, K. Treatment Failure with Propranolol for Subglottic Haemangioma. BMJ Case Rep. 2019, 12 (5), e227135. https://doi.org/10.1136/bcr-2018-227135.

(194) Park, H. J.; Lee, S.-Y.; Rho, M. H.; Jung, H. L. Ultrasound and MRI Findings as Predictors of Propranolol Therapy Response in Patients with Infantile Hemangioma. PloS One 2021, 16 (3), e0247505. https://doi.org/10.1371/journal.pone.0247505.

(195) Pottegård, A.; Kristensen, K. B.; Ernst, M. T.; Johansen, N. B.; Quartarolo, P.; Hallas, J. Use of N-Nitrosodimethylamine (NDMA) Contaminated Valsartan Products and Risk of Cancer: Danish Nationwide Cohort Study. BMJ 2018, 362, k3851. https://doi.org/10.1136/bmj.k3851.

(196) Pottegård, A.; Pedersen, S. A.; Schmidt, S. A. J.; Lee, C.-N.; Hsu, C.-K.; Liao, T.-C.; Shao, S.-C.; Lai, E. C.-C. Use of Hydrochlorothiazide and Risk of Skin Cancer: A Nationwide Taiwanese Case-Control Study. Br. J. Cancer 2019, 121 (11), 973–978. https://doi.org/10.1038/s41416-019-0613-4.

(197) Higuchi, S.; Takagi, M.; Hasegawa, Y. Use of Liothyronine without Levothyroxine in the Treatment of Mild Consumptive Hypothyroidism Caused by Hepatic Hemangiomas. Endocr. J. 2017, 64 (6), 639–643. https://doi.org/10.1507/endocrj.EJ16-0559.

(198) Small, W.; James, J. L.; Moore, T. D.; Fintel, D. J.; Lutz, S. T.; Movsas, B.; Suntharalingam, M.; Garces, Y. I.; Ivker, R.; Moulder, J.; Pugh, S.; Berk, L. B. Utility of the ACE Inhibitor Captopril in Mitigating Radiation-Associated Pulmonary Toxicity in Lung Cancer: Results From NRG Oncology RTOG 0123. Am. J. Clin. Oncol. 2018, 41 (4), 396–401. https://doi.org/10.1097/COC.0000000000000289.

(199) Li, J.; Lam, A. S. M.; Yau, S. T. Y.; Yiu, K. K. L.; Tsoi, K. K. F. Antihypertensive Treatments and Risks of Lung Cancer: A Large Population-Based Cohort Study in Hong Kong. BMC Cancer 2021, 21 (1), 1202. https://doi.org/10.1186/s12885-021-08971-6.

(200) Hüttner, F. J.; Klotz, R.; Giese, N. A.; Kong, B.; Ahmed, A.; Merz, D.; Pöchmann, A.; Burghaus, I.; Hackert, T.; Strobel, O.; Mihaljevic, A. L.; Michalski, C. W.; Büchler, M. W.; Diener, M. K. Pancreatic Resection with Perioperative Drug Repurposing of Propranolol and Etodolac - the Phase II Randomized Controlled PROSPER Trial. Langenbecks Arch. Surg. 2025, 410 (1), 168. https://doi.org/10.1007/s00423-025-03735-3.

(201) Shaashua, L.; Shabat-Simon, M.; Haldar, R.; Matzner, P.; Zmora, O.; Shabtai, M.; Sharon, E.; Allweis, T.; Barshack, I.; Hayman, L.; Arevalo, J.; Ma, J.; Horowitz, M.; Cole, S.; Ben-Eliyahu, S. Perioperative COX-2 and β-Adrenergic Blockade Improves Metastatic Biomarkers in Breast Cancer Patients in a Phase-II Randomized Trial. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2017, 23 (16), 4651–4661. https://doi.org/10.1158/1078-0432.CCR-17-0152.

(202) Neumann, E.; Klaiber, P.; Freitag, K.; Schwab, M.; Schaeffeler, E.; Hennenlotter, J.; Fend, F.; Kruck, S.; Scharpf, M.; Stenzl, A.; Bedke, J.; Rausch, S. Assessment of Concomitant Non-Oncologic Medication in Patients with Surgically Treated Renal Cell Carcinoma: Impact on Prognosis, Cell-Cycle Progression and Proliferation. J. Cancer Res. Clin. Oncol. 2019, 145 (7), 1835–1843. https://doi.org/10.1007/s00432-019-02914-2.

(203) Streekstra, E. J.; Keuper-Navis, M.; van den Heuvel, J. J. M. W.; van den Broek, P.; Stommel, M. W. J.; de Boode, W.; Botden, S.; Bervoets, S.; O’Gorman, L.; Greupink, R.; Russel, F. G. M.; van de Steeg, E.; de Wildt, S. N. Enteroids to Study Pediatric Intestinal Drug Transport. Mol. Pharm. 2024, 21 (10), 4983–4994. https://doi.org/10.1021/acs.molpharmaceut.4c00339.

(204) Seckl, M. J.; Ottensmeier, C. H.; Cullen, M.; Schmid, P.; Ngai, Y.; Muthukumar, D.; Thompson, J.; Harden, S.; Middleton, G.; Fife, K. M.; Crosse, B.; Taylor, P.; Nash, S.; Hackshaw, A. Multicenter, Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Pravastatin Added to First-Line Standard Chemotherapy in Small-Cell Lung Cancer (LUNGSTAR). J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2017, 35 (14), 1506–1514. https://doi.org/10.1200/JCO.2016.69.7391.

(205) Chopra, I.; Dwibedi, N.; Mattes, M. D.; Tan, X.; Findley, P.; Sambamoorthi, U. Nonadherence to Statins and Antihypertensives and Hospitalizations Among Elderly Medicare Beneficiaries With Incident Cancer. J. Natl. Compr. Cancer Netw. JNCCN 2017, 15 (11), 1351–1360. https://doi.org/10.6004/jnccn.2017.0168.

(206) Shen, X.; Fan, G.; Liu, G.; Wang, F.; Li, Q.; Liu, X.; Zhu, H.; Zhu, Y.; Lu, J.; Wang, S. Severe Adverse Cutaneous Reactions Induced by Gefitinib Combined with Antihypertensive and Antihyperlipidemic Drugs in Lung Cancer: A Case Report. Anticancer. Drugs 2022, 33 (1), e802–e807. https://doi.org/10.1097/CAD.0000000000001226.

(207) Budillon, A.; Leone, A.; Passaro, E.; Silvestro, L.; Foschini, F.; Iannelli, F.; Roca, M. S.; Macchini, M.; Bruzzese, F.; Garcia Bermejo, M. L.; Rodriguez Garrote, M.; Tortora, G.; Milella, M.; Reni, M.; Fuchs, C.; Hewitt, E.; Kubiak, C.; Di Gennaro, E.; Giannarelli, D.; Avallone, A. Randomized Phase 2 Study of Valproic Acid Combined with Simvastatin and Gemcitabine/Nab-Paclitaxel-Based Regimens in Untreated Metastatic Pancreatic Adenocarcinoma Patients: The VESPA Trial Study Protocol. BMC Cancer 2024, 24 (1), 1167. https://doi.org/10.1186/s12885-024-12936-w.

(208) Gao, Y.; Li, L.; Li, T.; Ma, L.; Yuan, M.; Sun, W.; Cheng, H. L.; Niu, L.; Du, Z.; Quan, Z.; Fan, Y.; Fan, J.; Luo, C.; Wu, X. Simvastatin Delays Castration‑resistant Prostate Cancer Metastasis and Androgen Receptor Antagonist Resistance by Regulating the Expression of Caveolin‑1. Int. J. Oncol. 2019, 54 (6), 2054–2068. https://doi.org/10.3892/ijo.2019.4774.

(209) Couttenier, A.; Lacroix, O.; Vaes, E.; Cardwell, C. R.; De Schutter, H.; Robert, A. Statin Use Is Associated with Improved Survival in Ovarian Cancer: A Retrospective Population-Based Study. PloS One 2017, 12 (12), e0189233. https://doi.org/10.1371/journal.pone.0189233.

(210) Hashem, J.; Alsukhni, F.; Abushukair, H.; Ayesh, M. The Effect of Atorvastatin on Oncogenic miRNAs in Hematological Malignancies: A Central Study. Biomolecules 2024, 14 (12), 1559. https://doi.org/10.3390/biom14121559.

(211) Kamal, A.; Boerner, J.; Assad, H.; Chen, W.; Simon, M. S. The Effect of Statins on Markers of Breast Cancer Proliferation and Apoptosis in Women with In Situ or Early-Stage Invasive Breast Cancer. Int. J. Mol. Sci. 2024, 25 (17), 9587. https://doi.org/10.3390/ijms25179587.

(212) Series, D. Q. N. C. Colorectal Cancer–Is Aspirin Any Good in Prevention?

(213) Novin, K.; Mortazavi, N.; Fadavi, P. Non-Randomized Controlled Trial Comparing Response of Rectal Cancer Chemoradiation with and without Low-Dose Aspirin. Med. J. Islam. Repub. Iran 2025, 39, 44.

(214) Mädge, J. C.; Stallmach, A.; Kleebusch, L.; Schlattmann, P. Meta-Analysis of Aspirin-Guided Therapy of Colorectal Cancer. J. Cancer Res. Clin. Oncol. 2022, 148 (6), 1407–1417. https://doi.org/10.1007/s00432-022-03942-1.

(215) Elwood, P. C.; Pickering, J. E.; Morgan, G.; Galante, J.; Weightman, A. L.; Morris, D.; Longley, M.; Mason, M.; Adams, R.; Dolwani, S. Systematic Review Update of Observational Studies Further Supports Aspirin Role in Cancer Treatment: Time to Share Evidence and Decision-Making with Patients? PLoS One 2018, 13 (9), e0203957.

(216) Tsakiridis, T.; Pond, G. R.; Wright, J.; Ellis, P. M.; Ahmed, N.; Abdulkarim, B.; Roa, W.; Robinson, A.; Swaminath, A.; Okawara, G. Metformin in Combination with Chemoradiotherapy in Locally Advanced Non–Small Cell Lung Cancer: The OCOG-ALMERA Randomized Clinical Trial. JAMA Oncol. 2021, 7 (9), 1333–1341.

(217) Skinner, H.; Hu, C.; Tsakiridis, T.; Santana-Davila, R.; Lu, B.; Erasmus, J. J.; Doemer, A. J.; Videtic, G. M.; Coster, J.; Yang, A. X. Addition of Metformin to Concurrent Chemoradiation in Patients with Locally Advanced Non–Small Cell Lung Cancer: The NRG-LU001 Phase 2 Randomized Clinical Trial. JAMA Oncol. 2021, 7 (9), 1324–1332.

(218) Lawrence, L. Home Evolving Standards of Care Possible Benefits of Metformin for Lung Cancer Still Unknown.

(219) Eze, C.; Belka, C.; Manapov, F. Forging a Path for Metformin Use in Inoperable Locally Advanced Non–Small Cell Lung Cancer. JAMA Oncol. 2021, 7 (9), 1341–1342.

(220) Chen, H.-F.; Lin, R.; Hsu, C.-X. Addition of Metformin to Non-Small-Cell Lung Cancer Patients with or without Diabetes. Thorac. Cancer 2022, 14 (2), 218.

(221) Feng, M.; Dai, X.; Yang, C.; Zhang, Y.; Tian, Y.; Qu, Q.; Sheng, M.; Li, Z.; Peng, X.; Cen, S. Unification of Medicines and Excipients: The Roles of Natural Excipients for Promoting Drug Delivery. Expert Opin. Drug Deliv. 2023, 20 (5), 597–620.

(222) Shaashua, L.; Shabat-Simon, M.; Haldar, R.; Matzner, P.; Zmora, O.; Shabtai, M.; Sharon, E.; Allweis, T.; Barshack, I.; Hayman, L. Perioperative COX-2 and β-Adrenergic Blockade Improves Metastatic Biomarkers in Breast Cancer Patients in a Phase-II Randomized Trial. Clin. Cancer Res. 2017, 23 (16), 4651–4661.

(223) Cronin-Fenton, D. P.; Heide-Jørgensen, U.; Ahern, T. P.; Lash, T. L.; Christiansen, P.; Ejlertsen, B.; Sørensen, H. T. Low-Dose Aspirin, Nonsteroidal Anti-Inflammatory Drugs, Selective COX-2 Inhibitors and Breast Cancer Recurrence. Epidemiology 2016, 27 (4), 586–593.

(224) Hiller, J. G.; Cole, S. W.; Crone, E. M.; Byrne, D. J.; Shackleford, D. M.; Pang, J.-M. B.; Henderson, M. A.; Nightingale, S. S.; Ho, K. M.; Myles, P. S. Preoperative β-Blockade with Propranolol Reduces Biomarkers of Metastasis in Breast Cancer: A Phase II Randomized Trial. Clin. Cancer Res. 2020, 26 (8), 1803–1811.

(225) Zhang, R.; Yin, H.; Yang, M.; Liu, J.; Zhen, D.; Zhang, Z. Advanced Progress of the Relationship between Renin–Angiotensin–Aldosterone System Inhibitors and Cancers. J. Hypertens. 2024, 42 (11), 1862–1873.

(226) Pawlonka, J.; Buchalska, B.; Buczma, K.; Borzuta, H.; Kamińska, K.; Cudnoch-Jędrzejewska, A. Targeting the Renin–Angiotensin–Aldosterone System (RAAS) for Cardiovascular Protection and Enhanced Oncological Outcomes: Review. Curr. Treat. Options Oncol. 2024, 25 (11), 1406–1427. https://doi.org/10.1007/s11864-024-01270-9.

(227) Rachow, T.; Schiffl, H.; Lang, S. M. Risk of Lung Cancer and Renin–Angiotensin Blockade: A Concise Review. J. Cancer Res. Clin. Oncol. 2021, 147 (1), 195–204. https://doi.org/10.1007/s00432-020-03445-x.

(228) Sun, Y.; Yin, Z.; Wu, L.; Yue, C.; Zhang, Y.; Subudhi, S.; Lei, P.; Muzikansky, A.; Zhang, L.; Rueda, B. R. Losartan Rewires Ovarian Cancer Tumor-Immune Microenvironment and Suppresses IGF-1 to Amplify Chemo-Immunotherapy Sensitivity. bioRxiv 2023, 2023–08.

(229) Sun, Y.; Yin, Z.; Li, S.; Wu, L.; Zhang, Y.; Zhao, Y.; Gomes dos Santos, I. L.; Subudhi, S.; Lei, P.; Muzikansky, A. Losartan Rewires the Tumor-Immune Microenvironment and Suppresses IGF-1 to Overcome Resistance to Chemo-Immunotherapy in Ovarian Cancer. Br. J. Cancer 2024, 131 (10), 1683–1693.

(230) Li, X.; Luo, X.; Hu, S. Modulating the Tumor Microenvironment Improves Antitumor Effect of Anti-PD-L1 mAb in Breast Cancer. BioImpacts BI 2023, 13 (2), 89.

(231) Dwairy, M.; Yehya, A.; Mohammad, F. M.; Alzoubi, H. Losartan as a Mechanotherapeutic Adjuvant: Remodeling the Breast Tumor Microenvironment to Improve Treatment Efficacy. Plos One 2025, 20 (7), e0328196.

(232) Saengboonmee, C.; Sanlung, T.; Wongkham, S. Repurposing Metformin for Cancer Treatment: A Great Challenge of a Promising Drug. Anticancer Res. 2021, 41 (12), 5913–5918.

(233) Gong, T.-T.; Wu, Q.-J.; Lin, B.; Ruan, S.-K.; Kushima, M.; Takimoto, M. Observational Studies on the Association between Post-Diagnostic Metformin Use and Survival in Ovarian Cancer: A Systematic Review and Meta-Analysis. Front. Oncol. 2019, 9, 458.

(234) Brancher, S.; Ribeiro, A. E.; Toporcov, T. N.; Weiderpass, E. The Role of Metformin on Lung Cancer Survival: The First Systematic Review and Meta-Analysis of Observational Studies and Randomized Clinical Trials. J. Cancer Res. Clin. Oncol. 2021, 147 (10), 2819–2836. https://doi.org/10.1007/s00432-021-03728-x.

(235) Robinson, E.; Nandi, M.; Wilkinson, L. L.; Arrowsmith, D. M.; Curtis, A. D.; Richardson, A. Preclinical Evaluation of Statins as a Treatment for Ovarian Cancer. Gynecol. Oncol. 2013, 129 (2), 417–424.

(236) Mohammadian-Hafshejani, A.; Sherwin, C. M.; Heidari-Soureshjani, S. Do Statins Play Any Role in Reducing the Incidence and Mortality of Ovarian Cancer? A Systematic Review and Meta-Analysis. J. Prev. Med. Hyg. 2020, 61 (3), E331.

(237) Khan, M. S.; Fatima, K.; Rameez. Impact of Statins on Risk and Survival of Ovarian Cancer. J. Gynecol. Oncol. 2015, 26 (3), 240. https://doi.org/10.3802/jgo.2015.26.3.240.

(238) Elmore, R. G.; Ioffe, Y.; Scoles, D. R.; Karlan, B. Y.; Li, A. J. Impact of Statin Therapy on Survival in Epithelial Ovarian Cancer. Gynecol. Oncol. 2008, 111 (1), 102–105.

(239) Couttenier, A.; Lacroix, O.; Vaes, E.; Cardwell, C. R.; De Schutter, H.; Robert, A. Statin Use Is Associated with Improved Survival in Ovarian Cancer: A Retrospective Population-Based Study. PloS One 2017, 12 (12), e0189233.

(240) Pottegård, A.; Pedersen, S. A.; Schmidt, S. A. J.; Lee, C.-N.; Hsu, C.-K.; Liao, T.-C.; Shao, S.-C.; Lai, E. C.-C. Use of Hydrochlorothiazide and Risk of Skin Cancer: A Nationwide Taiwanese Case–Control Study. Br. J. Cancer 2019, 121 (11), 973–978.

(241) Pottegård, A.; Pedersen, S. A.; Schmidt, S. A. J.; Hölmich, L. R.; Friis, S.; Gaist, D. Association of Hydrochlorothiazide Use and Risk of Malignant Melanoma. JAMA Intern. Med. 2018, 178 (8), 1120–1122.

(242) Pottegård, A.; Gaist, D. Hydrochlorothiazide and the Risk of Malignant Melanoma—Reply. JAMA Intern. Med. 2018, 178 (10), 1425–1426.

(243) Pedersen, S. A.; Schmidt, S. A. J.; Hölmich, L. R.; Friis, S.; Pottegård, A.; Gaist, D. Hydrochlorothiazide Use and Risk for Merkel Cell Carcinoma and Malignant Adnexal Skin Tumors: A Nationwide Case-Control Study. J. Am. Acad. Dermatol. 2019, 80 (2), 460–465.

(244) Pedersen, S. A.; Gaist, D.; Schmidt, S. A. J.; Hölmich, L. R.; Friis, S.; Pottegård, A. Hydrochlorothiazide Use and Risk of Nonmelanoma Skin Cancer: A Nationwide Case-Control Study from Denmark. J. Am. Acad. Dermatol. 2018, 78 (4), 673–681.

(245) Peng, Y.; Lyu, P.; Peng, X. Improving Research Transparency: An Interpretation of the Updated Consolidated Standards of Reporting Trials 2025 Guideline from the Perspective of Clinical Trials in Oncology. Cancer Pathog. Ther. 2025, S2949713225000795. https://doi.org/10.1016/j.cpt.2025.07.002.

(246) Shah, S. Common Terminology Criteria for Adverse Events. Natl. Cancer Inst. USA 2022, 784, 785.

(247) Freites-Martinez, A.; Santana, N.; Arias-Santiago, S.; Viera, A. Using the Common Terminology Criteria for Adverse Events (CTCAE–Version 5.0) to Evaluate the Severity of Adverse Events of Anticancer Therapies. Actas Dermo-Sifiliográficas Engl. Ed. 2021, 112 (1), 90–92.

(248) Puijk, R. S.; Ahmed, M.; Adam, A.; Arai, Y.; Arellano, R.; De Baère, T.; Bale, R.; Bellera, C.; Binkert, C. A.; Brace, C. L.; Breen, D. J.; Brountzos, E.; Callstrom, M. R.; Carrafiello, G.; Chapiro, J.; De Cobelli, F.; Coupé, V. M. H.; Crocetti, L.; Denys, A.; Dupuy, D. E.; Erinjeri, J. P.; Filippiadis, D.; Gangi, A.; Gervais, D. A.; Gillams, A. R.; Greene, T.; Guiu, B.; Helmberger, T.; Iezzi, R.; Kang, T. W.; Kelekis, A.; Kim, H. S.; Kröncke, T.; Kwan, S.; Lee, M. W.; Lee, F. T.; Lee, E. W.; Liang, P.; Lissenberg-Witte, B. I.; Lu, D. S.; Madoff, D. C.; Mauri, G.; Meloni, M. F.; Morgan, R.; Nadolski, G.; Narayanan, G.; Newton, I.; Nikolic, B.; Orsi, F.; Pereira, P. L.; Pua, U.; Rhim, H.; Ricke, J.; Rilling, W.; Salem, R.; Scheffer, H. J.; Sofocleous, C. T.; Solbiati, L. A.; Solomon, S. B.; Soulen, M. C.; Sze, D.; Uberoi, R.; Vogl, T. J.; Wang, D. S.; Wood, B. J.; Goldberg, S. N.; Meijerink, M. R. Consensus Guidelines for the Definition of Time-to-Event End Points in Image-Guided Tumor Ablation: Results of the SIO and DATECAN Initiative. Radiology 2021, 301 (3), 533–540. https://doi.org/10.1148/radiol.2021203715.

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2025-10-15
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ZONGO L, ZOHONCON TM, DEMBELE BT, LANGE H, CANFUA RR, BEMBAMBA DP-W, et al. Effectiveness and Safety of Common Non-Oncologic Pharmaceuticals in Cancer Management: A Systematic Review. J. Drug Delivery Ther. [Internet]. 2025 Oct. 15 [cited 2025 Nov. 10];15(10):304-67. Available from: https://jddtonline.info/index.php/jddt/article/view/7415

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Vol. 15 No. 10 (2025): Volume 15, Issue 10, October 2025

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Review

Copyright (c) 2025 Luc ZONGO , Théodora M. ZOHONCON, Bakary Tientigui DEMBELE, Heiko LANGE, Rosemary R. CANFUA, Davy P-W BEMBAMBA, Yilédoma T. M. LENGANE, Wilfried F. P. TRAORE, Lucien KABORE, Michel PALUKU MUKULULI, Raogo OUEDRAOGO, Mimtiri S. ZONGO, Esther Hortence Murielle DINA BELL, Modeste W. OUEDRAOGO, Arsène OUEDRAOGO, Jacques SIMPORE

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How to Cite

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ZONGO L, ZOHONCON TM, DEMBELE BT, LANGE H, CANFUA RR, BEMBAMBA DP-W, et al. Effectiveness and Safety of Common Non-Oncologic Pharmaceuticals in Cancer Management: A Systematic Review. J. Drug Delivery Ther. [Internet]. 2025 Oct. 15 [cited 2025 Nov. 10];15(10):304-67. Available from: https://jddtonline.info/index.php/jddt/article/view/7415
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