He Yu, Li Huan, Ju Xueming, Gong Bo
Human Disease Genes Key Laboratory of Sichuan Province and Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Human Disease Genes Key Laboratory of Sichuan Province and Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Biochim Biophys Acta Rev Cancer. 2024 Nov;1879(6):189212. doi: 10.1016/j.bbcan.2024.189212. Epub 2024 Nov 8.
Cancer drug resistance is a major obstacle to the effectiveness of chemoradiotherapy, targeted therapy, and immunotherapy. CRISPR/Cas9 library screening has emerged as a powerful genetic screening tool with significant potential to address this challenge. This review provides an overview of the development, methodologies, and applications of CRISPR/Cas9 library screening in the study of cancer drug resistance. We explore its role in elucidating resistance mechanisms, identifying novel anticancer targets, and optimizing treatment strategies. The use of in vivo single-cell CRISPR screens is also highlighted for their capacity to reveal T-cell regulatory networks in cancer immunotherapy. Challenges in clinical translation are discussed, including off-target effects, complexities in data interpretation, and model selection. Despite these obstacles, continuous technological advancements indicate a promising future for CRISPR/Cas9 library screening in overcoming cancer drug resistance.
癌症耐药性是放化疗、靶向治疗和免疫治疗有效性的主要障碍。CRISPR/Cas9文库筛选已成为一种强大的基因筛选工具,在应对这一挑战方面具有巨大潜力。本文综述了CRISPR/Cas9文库筛选在癌症耐药性研究中的发展、方法及应用。我们探讨了其在阐明耐药机制、识别新型抗癌靶点及优化治疗策略方面的作用。还强调了体内单细胞CRISPR筛选在揭示癌症免疫治疗中T细胞调节网络方面的能力。讨论了临床转化中的挑战,包括脱靶效应、数据解读的复杂性和模型选择。尽管存在这些障碍,但持续的技术进步表明CRISPR/Cas9文库筛选在克服癌症耐药性方面前景广阔。