Beyond Current Therapies: In Silico Drug Repurposing as a Strategy to Overcome Tyrosine Kinase Inhibitor Resistance in NSCLC

Authors

  • Sanae Baghrous Laboratory of Scientific and Clinical Research in Cancer Pathologies https://orcid.org/0009-0004-4877-7043
  • Ikram Ghicha Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Morocco. Laboratory of Scientific and Clinical Research in Cancer Pathologies, CEDoc UH2 https://orcid.org/0009-0009-2848-2033
  • Fatiha Bousselham Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Morocco. Laboratory of Scientific and Clinical Research in Cancer Pathologies, CEDoc UH2 https://orcid.org/0009-0001-1050-1154
  • Roussaint Doussou-Yovo Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Morocco. Laboratory of Scientific and Clinical Research in Cancer Pathologies, CEDoc UH2 https://orcid.org/0009-0000-5409-8275
  • Hasnaa Bazhar Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Morocco. Laboratory of Scientific and Clinical Research in Cancer Pathologies, CEDoc UH2 https://orcid.org/0000-0001-9061-2673
  • Youness Kadil Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Morocco. Laboratory of Scientific and Clinical Research in Cancer Pathologies, CEDoc UH2 https://orcid.org/0000-0001-8011-5120
  • Imane Rahmoune Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Morocco. Laboratory of Scientific and Clinical Research in Cancer Pathologies, CEDoc UH2 https://orcid.org/0000-0002-1980-0214
  • Houda Filali Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Morocco. Laboratory of Scientific and Clinical Research in Cancer Pathologies, CEDoc UH2 https://orcid.org/0000-0003-1563-2505

Abstract

Tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer (NSCLC) poses a major challenge to the long-term success of current targeted treatments. This paper explores this clinical obstacle and advocates for In Silico drug repurposing as an essential, rapid strategy to discover new therapies for various resistance mechanisms, including mutations in EGFR, ALK, ROS1, and MET. By applying advanced computational techniques, combining extensive genomic and phenotypic data, and utilizing sophisticated machine learning, this method provides a transformative way to find new uses for existing drugs. This approach significantly reduces the long development times, high costs, and failure rates associated with traditional new drug discovery. Although preclinical results are promising and clinical efforts are underway, there are no approved repurposed drugs specifically targeting TKI resistance in NSCLC, which remains a significant therapeutic challenge. We highlight the need for focused research to turn In Silico findings into practical clinical solutions, broadening treatment options and improving patient care in NSCLC.

Keywords: In Silico Drug Repurposing, Tyrosine Kinase Inhibitor Resistance, Non-Small Cell Lung Cancer, Drug Resistance.

Keywords:

In Silico Drug Repurposing, Tyrosine Kinase Inhibitor Resistance, Non-Small Cell Lung Cancer, Drug Resistance

DOI

https://doi.org/10.22270/jddt.v15i8.7276

Author Biographies

Sanae Baghrous , Laboratory of Scientific and Clinical Research in Cancer Pathologies

Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Morocco. Laboratory of Scientific and Clinical Research in Cancer Pathologies, CEDoc UH2

Ikram Ghicha , Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Morocco. Laboratory of Scientific and Clinical Research in Cancer Pathologies, CEDoc UH2

Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Morocco. Laboratory of Scientific and Clinical Research in Cancer Pathologies, CEDoc UH2

Fatiha Bousselham , Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Morocco. Laboratory of Scientific and Clinical Research in Cancer Pathologies, CEDoc UH2

Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Morocco. Laboratory of Scientific and Clinical Research in Cancer Pathologies, CEDoc UH2

Roussaint Doussou-Yovo , Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Morocco. Laboratory of Scientific and Clinical Research in Cancer Pathologies, CEDoc UH2

Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Morocco. Laboratory of Scientific and Clinical Research in Cancer Pathologies, CEDoc UH2

Hasnaa Bazhar , Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Morocco. Laboratory of Scientific and Clinical Research in Cancer Pathologies, CEDoc UH2

Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Morocco. Laboratory of Scientific and Clinical Research in Cancer Pathologies, CEDoc UH2

Youness Kadil , Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Morocco. Laboratory of Scientific and Clinical Research in Cancer Pathologies, CEDoc UH2

Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Morocco. Laboratory of Scientific and Clinical Research in Cancer Pathologies, CEDoc UH2

Imane Rahmoune , Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Morocco. Laboratory of Scientific and Clinical Research in Cancer Pathologies, CEDoc UH2

Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Morocco. Laboratory of Scientific and Clinical Research in Cancer Pathologies, CEDoc UH2

Houda Filali , Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Morocco. Laboratory of Scientific and Clinical Research in Cancer Pathologies, CEDoc UH2

Laboratory of Pharmacology-Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Morocco. Laboratory of Scientific and Clinical Research in Cancer Pathologies, CEDoc UH2

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2025-08-15
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How to Cite

1.
Baghrous S, Ghicha I, Bousselham F, Doussou-Yovo R, Bazhar H, Kadil Y, et al. Beyond Current Therapies: In Silico Drug Repurposing as a Strategy to Overcome Tyrosine Kinase Inhibitor Resistance in NSCLC. J. Drug Delivery Ther. [Internet]. 2025 Aug. 15 [cited 2026 Jan. 28];15(8):207-16. Available from: https://jddtonline.info/index.php/jddt/article/view/7276

How to Cite

1.
Baghrous S, Ghicha I, Bousselham F, Doussou-Yovo R, Bazhar H, Kadil Y, et al. Beyond Current Therapies: In Silico Drug Repurposing as a Strategy to Overcome Tyrosine Kinase Inhibitor Resistance in NSCLC. J. Drug Delivery Ther. [Internet]. 2025 Aug. 15 [cited 2026 Jan. 28];15(8):207-16. Available from: https://jddtonline.info/index.php/jddt/article/view/7276