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Updated: Jun 26, 2025

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
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Targeting KRAS Oncogene for Patients With Colorectal Cancer: A New Step Toward Precision Medicine

Ibrahim Halil Sahin1,2, Turcin Saridogan3, Ruveyda Ayasun4

  • 1Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA.

JCO Oncology Practice
|May 13, 2024
PubMed

Insights

Targeting KRAS G12C mutations with covalent inhibitors shows promise for colorectal cancer (CRC) treatment. This review covers KRAS G12C therapies, other RAS inhibitors, and future strategies for RAS-mutant CRC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Development

Background:

  • KRAS mutations are key drivers in various solid tumors, posing significant therapeutic challenges due to the oncogene's structure.
  • Covalent KRAS inhibitors offer a novel approach by targeting KRAS G12C mutants, leading to clinical responses in patients with KRAS G12C-mutant solid tumors, including colorectal cancer (CRC).

Purpose of the Study:

  • To review recent clinical advancements in targeting KRAS G12C for KRAS G12C-mutant CRC management.
  • To provide an update on alternative RAS-targeting strategies and discuss future therapeutic directions for RAS-mutant CRC.

Main Methods:

  • Literature review of clinical trials and research on KRAS inhibitors and RAS-targeting therapies.
  • Analysis of the biological characteristics of RAS-mutant CRC and associated resistance mechanisms.

Main Results:

  • KRAS G12C inhibitors have demonstrated significant clinical efficacy in patients with KRAS G12C-mutant solid tumors, including CRC.
  • Ongoing clinical trials are investigating other allele-specific, panKRAS, and panRAS inhibitors.

Conclusions:

  • KRAS G12C inhibitors represent a significant therapeutic advance for KRAS G12C-mutant CRC.
  • Combining KRAS inhibitors with anti-EGFR therapy and exploring novel strategies are crucial for overcoming resistance and improving outcomes in RAS-mutant CRC.

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