Targeting KRAS in colorectal cancer (Review)

Zhang,Minjie; Wu,Dawei; Tang,Yu; Zhang,Li; Zhang,Shuquan; Li,Wei; Li,Ning; Yan,Xinhua

doi:10.3892/mco.2025.2873

Targeting KRAS in colorectal cancer (Review)

Authors:
- Minjie Zhang
- Dawei Wu
- Yu Tang
- Li Zhang
- Shuquan Zhang
- Wei Li
- Ning Li
- Xinhua Yan
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Affiliations: Clinical Trials Center, Luanzhou People's Hospital, Tangshan, Hebei 063700, P.R. China, Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
Published online on: July 3, 2025 https://doi.org/10.3892/mco.2025.2873
Article Number: 78

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Abstract

RAS genes play crucial roles in regulating important biological processes such as cell growth, differentiation, and apoptosis in normal cells. When RAS genes undergo mutations or abnormal expression, they can become oncogenic drivers, and the oncogenic mechanism of KRAS mutations which drive cancer progression is highly complex. Colorectal cancer carrying KRAS mutation genes often exhibits poor prognosis. Despite the advent of KRAS G12C inhibitors, monotherapy demonstrates suboptimal clinical efficacy in colorectal cancer, which is attributed to primary resistance and limited coverage of prevalent KRAS mutations (such as G12D and G12V). Notably, combinatorial regimens integrating KRASG12C inhibitors with EGFR monoclonal antibodies (such as cetuximab) have doubled objective response rates, highlighting synergistic therapeutic potential.

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