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Updated: May 9, 2025

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
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KRAS mutations in colorectal cancer: impacts on tumor microenvironment and therapeutic implications

Anita Emami1, Pouya Mahdavi Sharif1, Nima Rezaei1,2,3

  • 1Tehran University of Medical Sciences, Tehran, Iran.

Expert Opinion on Therapeutic Targets
|May 5, 2025
PubMed
Abstract

Insights

Targeting KRAS mutations in colorectal cancer (CRC) is crucial for new therapies. Novel strategies are being developed to overcome challenges and improve outcomes for advanced CRC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Colorectal cancer (CRC) remains a significant cause of cancer mortality despite declining incidence.
  • While immunotherapies and targeted therapies show promise, many CRC patients, especially those with advanced disease, have suboptimal outcomes.
  • KRAS mutations are prevalent in CRC and drive tumor progression, metastasis, and resistance to therapies.

Purpose of the Study:

  • To discuss the impact of KRAS mutations on the colorectal cancer tumor microenvironment.
  • To explore novel therapeutic strategies targeting KRAS signaling pathways and resistance mechanisms.
  • To highlight the challenges and potential of developing drugs against KRAS mutations.

Main Methods:

  • Review of current literature on KRAS mutations in colorectal cancer.
  • Analysis of the role of KRAS in tumor microenvironment modulation.
  • Discussion of emerging therapeutic strategies, including combination therapies.

Main Results:

  • KRAS mutations critically influence the tumor microenvironment and treatment responses in CRC.
  • Developing drugs targeting KRAS is challenging due to its structure and essential functions.
  • Pre-clinical and early clinical data suggest promise in combining KRAS inhibitors with other therapies.

Conclusions:

  • There is a significant unmet need for novel therapies for advanced colorectal cancer, particularly targeting KRAS mutations.
  • Overcoming drug resistance and targeting KRAS effectively requires innovative strategies.
  • Combining KRAS inhibitors with immunotherapies and targeted therapies holds promise for improving CRC patient outcomes.
Keywords:
Colorectal cancerKRASmetabolismsmall moleculetargeted therapytumor microenvironment

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