Translational Insights into Focal Adhesion Kinase Inhibition for Non-Small-Cell Lung Cancer

Authors

  • Lakshmi Thangavelu Center for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, India
  • Lakshmi Thangavelu Center for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, India
  • Moyad Shahwan Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman 346, United Arab Emirates
  • Mohit Rana Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
  • Kavita Goyal Department of Biotechnology, Graphic Era (Deemed to be University), Clement Town, Dehradun 248002, India
  • Gaurav Gupta Centre for Research Impact & Outcome-Chitkara College of Pharmacy, Chitkara University, Punjab, India
  • Susmita Sinha Department of Physiology, Enam Medical College and Hospital, 9/3 Parboti Nagar, Thana Road, Savar, Dhaka, Bangladesh
  • Rahnuma Ahmad Department of Physiology, Medical College for Women and Hospital, Dhaka, Bangladesh
  • Mainul Haque Independent Researcher. Former Professor of Pharmacology and Therapeutics in Malaysia and Bangladesh. Block: C, Road: 10, House: 266, Khilgaon, Dhaka 1219, Bangladesh

DOI:

https://doi.org/10.3329/bjms.v24i4.84668

Keywords:

Metastasis; angiogenesis; proliferation; microenvironment; resistance; invasion; oncogenesis; phosphorylation; Focal adhesion kinase; Non–Non-small-cell lung cancer.

Abstract

Lung cancer remains the leading cause of cancer mortality globally, with non-small-cell lung cancer (NSCLC) accounting for approximately 85% of cases. Focal adhesion kinase (FAK), a non-receptor tyrosine kinase encoded by Protein Tyrosine Kinase 2 (PTK2), integrates signals from integrins and growthfactor receptors to drive cell proliferation, survival, migration, and invasion. Aberrant FAK activation, resulting from gene amplification, overexpression, or crosstalk with receptor tyrosine kinases, contributes to tumor progression and therapeutic resistance. This review synthesizes mechanistic insights into FAK signaling and critically appraises the development of ATPcompetitive FAK inhibitors, including defactinib (VS-6063), GSK2256098 (a novel oral FAK), and VS-4718. We examine their pharmacodynamic effects, safety profiles, and preliminary efficacy when combined with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and immune checkpoint blockade. Key challenges and opportunities for clinical translation are addressed, including biomarker development for patient selection, optimization of combination regimens to overcome adaptive resistance, and strategies to integrate FAK-targeted therapies within existing treatment paradigms. By aligning molecular and clinical perspectives with global healthcare realities, this review aims to inform research priorities and facilitate the integration of FAK-targeted therapies into the management of NSCLC worldwide—a graphical abstract illustrated in Figure 1.

BJMS, Vol. 24 No. 04 October’25 Page : 1029-1049

Downloads

Download data is not yet available.
Abstract
15
PDF
11

Downloads

Published

2025-11-02

How to Cite

Thangavelu, L., Thangavelu, L., Shahwan, M., Rana, M., Goyal, K., Gupta, G., … Haque, M. (2025). Translational Insights into Focal Adhesion Kinase Inhibition for Non-Small-Cell Lung Cancer. Bangladesh Journal of Medical Science, 24(4), 1029–1049. https://doi.org/10.3329/bjms.v24i4.84668

Issue

Vol. 24 No. 4 (2025)

Section

Review Article

License

Copyright (c) 2025 Lakshmi Thangavelu, Lakshmi Thangavelu, Moyad Shahwan, Mohit Rana, Kavita Goyal, Gaurav Gupta, Susmita Sinha, Rahnuma Ahmad, Mainul Haque

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors who publish in the Bangladesh Journal of Medical Science agree to the following terms that:

  1. Authors retain copyright and grant Bangladesh Journal of Medical Science the right of first publication of the work.

  2. Creative Commons Licence
    Articles in Bangladesh Journal of Medical Science are licensed under a Creative Commons Attribution 4.0 International License CC BY-4.0.This license permits use, distribution and reproduction in any medium, provided the original work is properly cited.
  3. Authors are able to enter into separate, additional contractual arrangements for the distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
  4. Authors are permitted to post their work online (e.g., in institutional repositories or on their website) as it can lead to productive exchanges, as well as greater citation of published work.