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Lookup NU author(s): Dr Othman AlmusaimiORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Tyrosine kinase inhibitors (TKIs) have emerged as a leading targeted cancer therapy, reducing the side effects often seen with non-targeted treatments, especially the damage to healthy cells. To tackle resistance, typically caused by epidermal growth factor receptor (EGFR) mutations, four generations of TKIs have been developed. Each generation has shown improved effectiveness and fewer side effects, resulting in better patient outcomes. For example, patients on gefitinib, a first-generation TKI, experienced a progression-free survival (PFS) of 10 months compared to 5 months with conventional chemotherapy. Second-generation TKI afatinib outperformed erlotinib and extended PFS to 11.1 months compared to 6.9 months with cisplatin. Third-generation TKIs further increased survival to 38.6 months, compared to 31.8 months with first-generation TKIs. This progress demonstrates the ability of newer TKIs to overcome resistance, particularly the T790M mutation, while reducing adverse effects. Ongoing research focuses on overcoming resistance from newer mutations like C797S to further improve patient survival. These developments highlight the significant progress in TKI therapy and the continued effort to refine cancer treatment. Recent research in South Korea shows that third-generation TKIs are ineffective against non-small cell lung cancer (NSCLC) with the C797S mutation. Several trials have started showing promising in vitro and in vivo results, but more trials are needed before clinical approval. This review underscores notable advancements in the field of EGFR TKIs, offering a comprehensive analysis of their mechanisms of action and the progression of various TKI generations in response to resistance.
Author(s): Dickerson H, Diab A, Al Musaimi O
Publication type: Article
Publication status: Published
Journal: International Journal of Molecular Sciences
Year: 2024
Volume: 25
Issue: 18
Print publication date: 17/09/2024
Online publication date: 17/09/2024
Acceptance date: 16/09/2024
Date deposited: 11/10/2024
ISSN (print): 1661-6596
ISSN (electronic): 1422-0067
Publisher: MDPI AG
URL: https://doi.org/10.3390/ijms251810008
DOI: 10.3390/ijms251810008
Data Access Statement: Data sharing is not applicable.
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