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Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
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The promise and peril of KRAS G12C inhibitors

Amanda R Moore1, Shiva Malek1

  • 1Department of Discovery Oncology, Genentech Inc., South San Francisco, CA 94080, USA.

Cancer Cell
|August 10, 2021
PubMed

Insights

Sotorasib offers clinical benefits for KRAS p.G12C-mutated non-small-cell lung cancer (NSCLC). This study reveals how tumors develop resistance to KRASG12C-specific therapies, offering new insights.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • RAS mutant tumors, particularly KRAS mutations, are historically difficult to treat.
  • Targeted therapies for specific RAS mutations are an area of active research in oncology.

Purpose of the Study:

  • To evaluate the clinical benefit of sotorasib in patients with KRAS p.G12C-mutated non-small-cell lung cancer (NSCLC).
  • To elucidate the mechanisms of acquired resistance to KRASG12C-specific inhibition.

Main Methods:

  • Clinical trial evaluating sotorasib in NSCLC patients with KRAS p.G12C mutation.
  • Mechanistic studies to investigate acquired resistance pathways.

Main Results:

  • Sotorasib demonstrated clinical benefit in patients with KRAS p.G12C-mutated NSCLC.
  • Identified key mechanisms contributing to acquired resistance to sotorasib therapy.

Conclusions:

  • Sotorasib is a promising therapeutic option for a subset of NSCLC patients.
  • Understanding resistance mechanisms is crucial for overcoming treatment limitations in RAS-mutant cancers.

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