Drug Resistance Mechanisms and Strategies of EGFR/ALK Targeted Therapy in Non-Small Cell Lung Cancer

Yanwei Wang

doi:10.54254/2753-8818/2025.AU27101

Theoretical and Natural ScienceOpen access

Drug Resistance Mechanisms and Strategies of EGFR/ALK Targeted Therapy in Non-Small Cell Lung Cancer

Research Article

Open Access

Drug Resistance Mechanisms and Strategies of EGFR/ALK Targeted Therapy in Non-Small Cell Lung Cancer

Yanwei Wang ^1*

¹ Immersion Academy

^*Corresponding author: counselor@immersionacad.com

Published on 24 September 2025

TNS Vol.137

ISSN (Print): 2753-8826

ISSN (Online): 2753-8818

ISBN (Print): 978-1-80590-371-0

ISBN (Online): 978-1-80590-372-7

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Abstract

Non-small cell lung cancer (NSCLC) remains a leading cause of global cancer-related mortality. Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) targeted therapies have revolutionized the treatment of patients with corresponding mutations or fusions. However, the emergence of drug resistance—including primary resistance (e.g., EGFR exon 20 insertions, ALK fusion variant heterogeneity) and acquired resistance (e.g., EGFR T790M, ALK L1196M mutations)—severely limits long-term efficacy. This review systematically synthesizes the molecular mechanisms underlying EGFR/ALK resistance, highlighting both commonalities (e.g., target mutations) and specificities (e.g., small cell transformation in EGFR resistance). It further summarizes current coping strategies, including the development of next-generation inhibitors (osimertinib, lorlatinib), combination therapies (targeted therapy combined with chemotherapy, immunotherapy, or dual-target inhibition), and personalized regimens guided by liquid biopsy. Additionally, the review discusses recent research advances, ongoing challenges (complex resistance, toxicity management), and future directions (single-cell sequencing, multi-target drug design), aiming to provide insights for optimizing clinical practice and accelerating therapeutic innovation in NSCLC.

Keywords:

Non-small cell lung cancer, EGFR, ALK, targeted therapy, drug resistance, therapeutic strategies.

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References

[1]. Jeon, H., Wang, S., Song, J., Gill, H., & Cheng, H. (2025). Update 2025: Management of NonSmall-Cell Lung Cancer. Lung, 203(1), 53.

Cite this article

Wang,Y. (2025). Drug Resistance Mechanisms and Strategies of EGFR/ALK Targeted Therapy in Non-Small Cell Lung Cancer. Theoretical and Natural Science,137,33-39.

Data availability

The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.

About volume

Volume title: Proceedings of ICBioMed 2025 Symposium: AI for Healthcare: Advanced Medical Data Analytics and Smart Rehabilitation

ISBN: 978-1-80590-371-0(Print) / 978-1-80590-372-7(Online)

Editor: Alan Wang

Conference website: https://2025.icbiomed.org/auckland.html

Conference date: 17 October 2025

Series: Theoretical and Natural Science

Volume number: Vol.137

ISSN: 2753-8818(Print) / 2753-8826(Online)

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