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Updated: Jun 24, 2025

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Resistance to KRAS inhibition in advanced non-small cell lung cancer

Katherina Bernadette Sreter1, Maria Joana Catarata2,3, Maximilian von Laffert4

  • 1Department of Pulmonology, University Hospital Centre "Sestre Milosrdnice", Zagreb, Croatia.

Frontiers in Oncology
|June 7, 2024
PubMed

Insights

Targeted therapies for KRAS-mutated lung cancer show promise. New GTPase inhibitors offer improved outcomes for advanced non-small cell lung cancer (NSCLC) patients, with ongoing research addressing resistance mechanisms.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Lung cancer is a leading global cause of cancer death.
  • Over 50% of cases are diagnosed at advanced or metastatic stages, leading to poor survival.
  • KRAS mutations are common in lung adenocarcinoma but historically difficult to target.

Purpose of the Study:

  • To review the molecular basis of KRAS mutations in lung cancer.
  • To discuss the clinical evidence for KRAS inhibition.
  • To explore resistance mechanisms and future strategies for KRAS-targeted therapies.

Main Methods:

  • This is a narrative review.
  • Literature search on KRAS mutations, targeted therapies, and resistance.
  • Analysis of clinical trial data and scientific literature.

Main Results:

  • KRAS mutations are prevalent in lung adenocarcinoma.
  • Small molecule GTPase inhibitors show promising results in clinical trials.
  • Two targeted therapies (adagrasib, sotorasib) are approved for advanced NSCLC.

Conclusions:

  • Targeting KRAS mutations in lung cancer has become a viable therapeutic strategy.
  • Understanding co-mutations and resistance is crucial for optimizing treatment.
  • Future research should focus on overcoming resistance to KRAS inhibitors.
Keywords:
KRASco-mutationslung adenocarcinomanon-small cell lung cancerresistance to therapy

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