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Updated: Sep 17, 2025

Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
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Published on: September 8, 2023

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KRAS mutated NSCLC: past, present, and future directions in a rapidly evolving landscape

Austin Frisch1, Eric Martin1, So Yeon Kim2

  • 1Inova Fairfax Department of Internal Medicine, Inova Fairfax Hospital, Fairfax, VA 22042, United States.

The Oncologist
|June 30, 2025
PubMed

Insights

Targeting Kirsten rat sarcoma virus (KRAS) mutations in non-small cell lung cancer (NSCLC) offers new hope. This review explores current and future KRAS inhibitor treatments, including combination therapies, and discusses overcoming resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Precision Medicine

Background:

  • Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths globally.
  • The advent of precision medicine has revolutionized NSCLC treatment, focusing on oncogenic drivers and immunotherapy.
  • Kirsten rat sarcoma virus (KRAS) mutations are the most frequent in NSCLC, making it a key therapeutic target.

Purpose of the Study:

  • To provide a comprehensive review of KRAS-targeted therapies for NSCLC.
  • To discuss the evolution of KRAS inhibitor monotherapy and combinatorial approaches.
  • To highlight the molecular mechanisms, challenges (e.g., resistance), and future directions in KRAS-mutated NSCLC treatment.

Main Methods:

  • In-depth literature review of preclinical and clinical studies.
  • Analysis of molecular biology underpinning KRAS targeted therapy.
  • Examination of clinical trial data for KRAS inhibitor monotherapy and combination strategies.

Main Results:

  • KRAS inhibitors have emerged as a significant therapeutic strategy for NSCLC.
  • Combinatorial approaches, including immunotherapy, show promise in overcoming resistance.
  • Understanding KRAS molecular pathways is crucial for developing effective treatments.

Conclusions:

  • Targeted therapy for KRAS-mutated NSCLC has advanced significantly.
  • Overcoming treatment resistance remains a critical challenge requiring further research.
  • Future strategies will likely involve novel combination therapies and a deeper understanding of KRAS biology.
Keywords:
KRASNSCLCco-mutationresistancereview

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