KRAS Mutations in Cancer: Understanding Signaling Pathways to Immune Regulation and the Potential of Immunotherapy

Cancers (Basel). 2025 Feb 25;17(5):785. doi: 10.3390/cancers17050785.

Priyanka Uniyal ¹, Vivek Kumar Kashyap ² ³, Tapan Behl ⁴, Deepak Parashar ⁵, Ravi Rawat ¹

Affiliations

1 Department of Pharmaceutical Technology, School of Health Sciences and Technology, UPES, Dehradun 248007, India.
2 Division of Cancer Immunology and Microbiology, Medicine, and Oncology Integrated Service Unit, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA.
3 South Texas Center of Excellence in Cancer Research (ST-CECR), School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA.
4 Amity School of Pharmaceutical Sciences, Amity University, Mohali 140306, India.
5 Division of Hematology & Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

PMID: 40075634 DOI: 10.3390/cancers17050785

Abstract

The Kirsten rat sarcoma viral oncogene homologue (KRAS) mutation is one of the most prevailing mutations in various tumors and is difficult to cure. Long-term proliferation in carcinogenesis is primarily initiated by oncogenic KRAS-downstream signaling. Recent research suggests that it also activates the autocrine effect and interplays the tumor microenvironment (TME). Here, we discuss the emerging research, including KRAS mutations to immune evasion in TME, which induce immunological modulation that promotes tumor development. This review gives an overview of the existing knowledge of the underlying connection between KRAS mutations and tumor immune modulation. It also addresses the mechanisms to reduce the effect of oncogenes on the immune system and recent advances in clinical trials for immunotherapy in KRAS-mutated cancers.

Keywords

KRAS mutation; cancer; immunotherapy; oncogene; tumor microenvironment.

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