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Updated: Aug 8, 2025

Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer

Published on: September 8, 2023

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Treatment of advanced non-small cell lung cancer with driver mutations: current applications and future directions

Jia Zhong1, Hua Bai1, Zhijie Wang1

  • 1State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

Frontiers of Medicine
|February 27, 2023
PubMed

Insights

This review classifies non-small cell lung cancer (NSCLC) management based on driver mutations, exploring resistance mechanisms and the role of immune-checkpoint inhibitors (ICIs) for tailored treatments.

Area of Science:

  • Oncology
  • Genetics
  • Immunology

Background:

  • Targeted therapies have improved outcomes in non-small cell lung cancer (NSCLC) driven by specific mutations.
  • However, treatment responses are often temporary, incomplete, and variable among patients.
  • The efficacy of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC requires further clarification.

Purpose of the Study:

  • To classify NSCLC management strategies based on driver gene subtypes, mutations, and temporal changes.
  • To review mechanisms of resistance to targeted therapies, including target-dependent and target-independent pathways.
  • To discuss the effectiveness of ICIs and combination therapies in overcoming the tumor immune microenvironment in oncogene-driven NSCLC.

Main Methods:

  • Literature review and synthesis of current research on NSCLC driver mutations.
  • Classification of management strategies according to genetic profiles and resistance mechanisms.
  • Analysis of clinical data and preclinical studies on targeted therapies and ICIs.

Main Results:

  • Identified diverse resistance mechanisms to targeted therapies in NSCLC.
  • Highlighted the complex role and potential of ICIs in oncogene-driven NSCLC.
  • Outlined emerging treatment strategies for novel oncogenic alterations.

Conclusions:

  • Tailored treatment approaches are crucial for managing NSCLC with driver mutations.
  • Understanding resistance mechanisms and the tumor immune microenvironment is key to improving therapeutic efficacy.
  • This review provides a framework for personalized treatment design in NSCLC.
Keywords:
driver mutationsimmune-checkpoint inhibitorsnon-small cell lung cancerresistant mechanismtreatment strategy

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