文章：

CRISPR技术靶向KRAS：基础与转化癌症研究中的曲折之路与光明前景

CRISPRingKRAS: A Winding Road with a Bright Future in Basic and Translational Cancer Research

原文发布日期：22 January 2024

DOI: 10.3390/cancers16020460

类型: Article

开放获取: 是

英文摘要：

Once considered “undruggable” due to the strong affinity of RAS proteins for GTP and the structural lack of a hydrophobic “pocket” for drug binding, the development of proprietary therapies for KRAS-mutant tumors has long been a challenging area of research. CRISPR technology, the most successful gene-editing tool to date, is increasingly being utilized in cancer research. Here, we provide a comprehensive review of the application of the CRISPR system in basic and translational research in KRAS-mutant cancer, summarizing recent advances in the mechanistic understanding of KRAS biology and the underlying principles of drug resistance, anti-tumor immunity, epigenetic regulatory networks, and synthetic lethality co-opted by mutant KRAS.

摘要翻译： 

由于RAS蛋白与GTP的高亲和力及其结构上缺乏可供药物结合的疏水性“口袋”，KRAS突变肿瘤的靶向疗法开发曾长期被视为“不可成药”的研究难题。CRISPR技术作为迄今最成功的基因编辑工具，正日益广泛应用于癌症研究领域。本文系统综述了CRISPR系统在KRAS突变癌症基础与转化研究中的应用，重点总结了该技术在解析KRAS生物学机制、揭示耐药原理、阐明抗肿瘤免疫机制、探索表观遗传调控网络以及发现突变KRAS介导的合成致死效应等方面的最新进展。

原文链接：

CRISPRingKRAS: A Winding Road with a Bright Future in Basic and Translational Cancer Research