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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Molecular pathways, resistance mechanisms and targeted interventions in non-small-cell lung cancer
Zixi Wang1, Yurou Xing1, Bingjie Li1
1Thoracic Oncology Ward, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Abstract:
Lung cancer is the leading cause of cancer-related mortality worldwide. The discovery of tyrosine kinase inhibitors effectively targeting EGFR mutations in lung cancer patients in 2004 represented the beginning of the precision medicine era for this refractory disease. This great progress benefits from the identification of driver gene mutations, and after that, conventional and new technologies such as NGS further illustrated part of the complex molecular pathways of NSCLC. More targetable driver gene mutation identification in NSCLC patients greatly promoted the development of targeted therapy and provided great help for patient outcomes including significantly improved survival time and quality of life. Herein, we review the literature and ongoing clinical trials of NSCLC targeted therapy to address the molecular pathways and targeted intervention progress in NSCLC. In addition, the mutations in EGFR gene, ALK rearrangements, and KRAS mutations in the main sections, and the less common molecular alterations in MET, HER2, BRAF, ROS1, RET, and NTRK are discussed. The main resistance mechanisms of each targeted oncogene are highlighted to demonstrate the current dilemma of targeted therapy in NSCLC. Moreover, we discuss potential therapies to overcome the challenges of drug resistance. In this review, we manage to display the current landscape of targetable therapeutic patterns in NSCLC in this era of precision medicine.
Insights
Precision medicine advances lung cancer treatment by targeting specific gene mutations like EGFR. This review details targeted therapies, their pathways, and challenges like drug resistance in non-small cell lung cancer (NSCLC).
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Lung cancer remains a leading cause of cancer mortality globally.
- The advent of tyrosine kinase inhibitors targeting EGFR mutations marked the start of precision medicine in lung cancer.
- Next-generation sequencing (NGS) has elucidated complex molecular pathways in non-small cell lung cancer (NSCLC).
Purpose of the Study:
- To review literature and clinical trials on targeted therapy for NSCLC.
- To discuss molecular pathways, targeted interventions, and resistance mechanisms in NSCLC.
- To highlight current progress and challenges in precision medicine for NSCLC.
Main Methods:
- Literature review of published studies on NSCLC targeted therapy.
- Analysis of ongoing clinical trials investigating targeted interventions.
- Discussion of genetic alterations, including EGFR, ALK, KRAS, MET, HER2, BRAF, ROS1, RET, and NTRK.
Main Results:
- Identification of numerous targetable driver gene mutations has significantly improved NSCLC patient outcomes.
- Targeted therapies offer improved survival time and quality of life for NSCLC patients.
- Key molecular alterations and their associated targeted therapies are discussed, alongside common resistance mechanisms.
Conclusions:
- Targeted therapy has transformed NSCLC treatment within the precision medicine framework.
- Drug resistance remains a significant challenge, necessitating the development of novel therapeutic strategies.
- Understanding molecular pathways and resistance mechanisms is crucial for advancing NSCLC targeted therapy.
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