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The Ras Gene02:38

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The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
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Related Experiment Video

Updated: Aug 1, 2025

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
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CodeBreak 200: Sotorasib Has Not Broken the KRASG12C Enigma Code.

Shannon S Zhang1, Alexandria Lee1, Misako Nagasaka1,2

  • 1University of California Irvine School of Medicine, Orange, CA, USA.

Lung Cancer (Auckland, N.Z.)
|April 27, 2023
PubMed
Summary

Sotorasib, a KRAS G12C inhibitor, showed improved progression-free survival in non-small cell lung cancer (NSCLC) patients compared to docetaxel. Further research is needed for KRAS G12C targeted therapies.

Keywords:
AMG 510CodeBreaK 100CodeBreaK 200KRASG12Cdocetaxelnon-small cell lung cancersotorasib

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Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • KRAS G12C mutation occurs in 13% of non-small cell lung cancer (NSCLC) patients.
  • Sotorasib is a targeted therapy approved for NSCLC with KRAS G12C mutation.
  • Previous trials showed promising response rates and progression-free survival (PFS) for sotorasib.

Purpose of the Study:

  • To evaluate the efficacy of sotorasib compared to docetaxel in patients with previously treated, advanced KRAS G12C-mutated NSCLC.
  • To assess progression-free survival (PFS) and safety of sotorasib in this patient population.

Main Methods:

  • CodeBreaK 200 is a Phase III trial comparing sotorasib to docetaxel.
  • Patients had locally advanced or unresectable metastatic KRAS G12C NSCLC, pretreated with chemotherapy and checkpoint inhibitors.

Main Results:

  • Sotorasib demonstrated a PFS of 5.6 months versus 4.5 months for docetaxel.
  • Adagrasib, another G12C inhibitor, received accelerated FDA approval with a 43% response rate.
  • Most adverse events with sotorasib were low-grade, commonly diarrhea and nausea.

Conclusions:

  • Sotorasib offers a survival benefit over docetaxel in previously treated KRAS G12C NSCLC.
  • The evolving landscape of KRAS G12C inhibitors presents new therapeutic opportunities.
  • Further investigation into novel agents and combinations is warranted to overcome resistance and improve outcomes.