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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
Diserahkan: 2 September 2024/Diterima: 18 Jun 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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*Pengarang untuk surat-menyurat; email: kumaylabdul@um.edu.my
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