1.Novel paradigms in KRAS targeting: Unveiling strategies to combat drug resistance.
Xiyuan LUO ; Feihan ZHOU ; Yuemeng TANG ; Xiaohong LIU ; Ruilin XIAO ; Minzhi GU ; Jialu BAI ; Decheng JIANG ; Gang YANG ; Lei YOU ; Yupei ZHAO
Chinese Medical Journal 2025;138(18):2243-2267
The Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutation is one of the most prevalent activating alterations in cancer. It indicates a poor overall prognosis due to its highly invasive nature. Although several KRAS inhibitors have been developed in recent years, a significant clinical challenge has emerged as a substantial proportion of patients eventually develop resistance to these therapies. Therefore, identifying determinants of drug resistance is critical for guiding treatment strategies. This review provides a comprehensive overview of the mutation landscape and molecular mechanisms of KRAS activity in various cancers. Meanwhile, it summaries the progress and prospects of small molecule KRAS inhibitors undergoing clinical trials. Furthemore, this review explores potential strategies to overcome drug resistance, with the ultimate goal of steering toward patient-centric precision oncology in the foreseeable future.
Humans
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Drug Resistance, Neoplasm/drug effects*
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Proto-Oncogene Proteins p21(ras)/metabolism*
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Mutation/genetics*
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Neoplasms/genetics*
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Antineoplastic Agents/therapeutic use*
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