Sains Malaysiana 54(8)(2025): 2021-2032

http://doi.org/10.17576/jsm-2025-5408-12

 

EGFR-Directed Tyrosine Kinase Inhibitors for Non-Small Cell Lung Cancer

(Perencat Tirosina Kinase EGFR Terarah untuk Kanser Paru-paru Bukan Sel Kecil)

 

FATIN NUR ELYANA MOHD SIDEK1, MUHAMMAD KUMAYL ABDULWAHAB1,*, RASHIDI DZUL KEFLEE2, MOHAMMED ABDULLAH ALSHAWSH3,4, SUZITA MOHD NOOR5, ZARIF MOHAMED SOFIAN6 & AZHAR ARIFFIN1

 

1Department of Chemistry, Faculty of Science, Universiti Malaya, 50603 Kuala Lumpur, Malaysia

2Department of Molecular Medicine, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia

3Department of Pharmacology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia

4School of Clinical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, 246 Clayton Road, Clayton, VIC, 3168, Australia

5Department of Biomedical Science, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia

6Department of Pharmaceutical Technology, Faculty of Pharmacy, Universiti Malaya, 50603 Kuala Lumpur, Malaysia

 

Received: 2 September 2024/Accepted: 18 June 2025

 

Abstract

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases and remains a leading cause of cancer-related deaths globally. While conventional chemotherapy has provided modest benefits, its toxicity and limited efficacy have underscored the need for more precise treatments. The identification of epidermal growth factor receptor (EGFR) mutations has transformed the therapeutic landscape, with EGFR tyrosine kinase inhibitors (EGFR-TKIs) significantly improving progression-free and overall survival in EGFR-mutant NSCLC. However, resistance mechanisms, such as T790M and C797S mutations have led to the development of successive generations of EGFR-TKIs. Fourth-generation inhibitors and combination therapies targeting bypass pathways now offer renewed hope for overcoming resistance. Nonetheless, the high cost and limited accessibility of these targeted therapies remain critical barriers, particularly in low- and middle-income countries. This review highlights the evolution of EGFR-TKIs, key resistance challenges, and economic considerations, emphasizing the need for equitable access to advance NSCLC treatment globally.

Keywords: EGFR; NSCLC; tyrosine-kinase inhibitors

 

Abstrak

Kanser paru-paru bukan sel kecil (NSCLC) menyumbang kira-kira 85% daripada semua kes kanser paru-paru dan kekal sebagai punca utama kematian berkaitan kanser di seluruh dunia. Walaupun kemoterapi konvensional telah memberikan faedah yang sederhana, ketoksikan dan keberkesanannya yang terhad telah menekankan keperluan untuk rawatan yang lebih tepat. Pengenalpastian mutasi reseptor faktor pertumbuhan epidermis (EGFR) telah mengubah landskap terapeutik dengan perencat tirosina kinase EGFR (EGFR-TKIs) dengan ketara meningkatkan kelangsungan hidup bebas perkembangan dan keseluruhan dalam NSCLC mutan EGFR. Walau bagaimanapun, mekanisme rintangan, seperti mutasi T790M dan C797S, telah membawa kepada pembangunan generasi berturut-turut EGFR-TKI. Perencat generasi keempat dan terapi gabungan yang menyasarkan laluan pintasan kini menawarkan harapan baharu untuk mengatasi rintangan. Namun begitu, kos tinggi dan akses terhad bagi terapi yang disasarkan ini kekal sebagai halangan kritikal, terutamanya di negara berpendapatan rendah dan sederhana. Kertas ini menyerlahkan evolusi EGFR-TKI, cabaran rintangan utama dan pertimbangan ekonomi, menekankan keperluan untuk akses yang saksama untuk memajukan rawatan NSCLC secara global.

Kata kunci: EGFR; NSCLC; perencat tirosina kinase

 

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*Corresponding author; email: kumaylabdul@um.edu.my

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 
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