Related Experiment Video

Updated: Jun 28, 2025

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Targeting KRAS in cancer

Anupriya Singhal1,2, Bob T Li3,4,5, Eileen M O'Reilly6,7,8

  • 1Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Nature Medicine
|April 18, 2024
PubMed

Insights

KRAS mutations drive many cancers. New therapies now target these previously undruggable mutations, offering hope for improved patient outcomes in various malignancies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • RAS family variants, particularly KRAS, are common cancer-driving mutations linked to poor prognosis.
  • KRAS has historically been considered undruggable due to its structure.
  • Recent scientific advancements enable direct targeting of KRAS.

Purpose of the Study:

  • To review RAS pathobiology with a focus on KRAS.
  • To illustrate therapeutic approaches for KRAS-targeted therapies.
  • To summarize resistance mechanisms and future directions in KRAS therapeutics.

Main Methods:

  • Review of scientific literature on RAS pathobiology and KRAS inhibitors.
  • Analysis of therapeutic strategies including allele-specific and pan-RAS inhibitors.
  • Examination of combination therapies, immunotherapeutics, and resistance mechanisms.

Main Results:

  • Successful allele-specific targeting of KRAS G12C in non-small cell lung cancer with approved agents (sotorasib, adagrasib).
  • Emerging inhibitors show activity against other KRAS variants in refractory cancers like pancreatic cancer.
  • Understanding of resistance mechanisms and development of combination strategies are advancing.

Conclusions:

  • Direct KRAS targeting is now a reality, with initial successes in specific mutations.
  • Diverse therapeutic strategies, including combination approaches, are being developed for broader KRAS targeting.
  • Future KRAS therapeutics hold significant clinical potential for cancer treatment.

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