Novel paradigms in KRAS targeting: Unveiling strategies to combat drug resistance.

IF 7.3 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

Chinese Medical Journal Pub Date : 2025-09-20 Epub Date: 2025-08-18 DOI:10.1097/CM9.0000000000003776

Xiyuan Luo, Feihan Zhou, Yuemeng Tang, Xiaohong Liu, Ruilin Xiao, Minzhi Gu, Jialu Bai, Decheng Jiang, Gang Yang, Lei You, Yupei Zhao

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引用次数: 0

Abstract

Abstract: 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.

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KRAS靶向的新范式：揭示对抗耐药性的策略。

摘要：Kirsten大鼠肉瘤病毒癌基因同源（KRAS）突变是癌症中最常见的激活改变之一。由于其高度侵袭性，它表明整体预后较差。尽管近年来已经开发了几种KRAS抑制剂，但由于相当大比例的患者最终对这些疗法产生耐药性，因此出现了重大的临床挑战。因此，确定耐药性的决定因素对于指导治疗策略至关重要。本文综述了KRAS在各种癌症中的突变情况和分子机制。同时，综述了KRAS小分子抑制剂的临床研究进展及前景。此外，本综述探讨了克服耐药的潜在策略，最终目标是在可预见的未来转向以患者为中心的精确肿瘤学。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Chinese Medical Journal 医学-医学：内科

CiteScore

9.80

自引率

4.90%

发文量

19245

审稿时长

6 months

期刊介绍： The Chinese Medical Journal (CMJ) is published semimonthly in English by the Chinese Medical Association, and is a peer reviewed general medical journal for all doctors, researchers, and health workers regardless of their medical specialty or type of employment. Established in 1887, it is the oldest medical periodical in China and is distributed worldwide. The journal functions as a window into China’s medical sciences and reflects the advances and progress in China’s medical sciences and technology. It serves the objective of international academic exchange. The journal includes Original Articles, Editorial, Review Articles, Medical Progress, Brief Reports, Case Reports, Viewpoint, Clinical Exchange, Letter,and News,etc. CMJ is abstracted or indexed in many databases including Biological Abstracts, Chemical Abstracts, Index Medicus/Medline, Science Citation Index (SCI), Current Contents, Cancerlit, Health Plan & Administration, Embase, Social Scisearch, Aidsline, Toxline, Biocommercial Abstracts, Arts and Humanities Search, Nuclear Science Abstracts, Water Resources Abstracts, Cab Abstracts, Occupation Safety & Health, etc. In 2007, the impact factor of the journal by SCI is 0.636, and the total citation is 2315.