Evolution of Molecular Targeted Cancer Therapy: Mechanisms of Drug Resistance and Novel Opportunities Identified by CRISPR-Cas9 Screening

作者：Jue Hou, Zongsheng He, Tian Liu, Dongfeng Chen, Bin Wang, Qinglian Wen, Xi Zheng · 发表于：Frontiers in Oncology · 年份：2022 · DOI：10.3389/fonc.2022.755053 · 被引用次数：38 · 研究领域：CRISPR and Genetic Engineering、Innovative Microfluidic and Catalytic Techniques Innovation、CAR-T cell therapy research

Molecular targeted therapy has revolutionized the landscape of cancer treatment due to better therapeutic responses and less systemic toxicity. However, therapeutic resistance is a major challenge in clinical settings that hinders continuous clinical benefits for cancer patients. In this regard, unraveling the mechanisms of drug resistance may identify new druggable genetic alterations for molecularly targeted therapies, thus contributing to improved therapeutic efficacies. The recent rapid development of novel methodologies including CRISPR-Cas9 screening technology and patient-derived models provides powerful tools to dissect the underlying mechanisms of resistance to targeted cancer therapies. In this review, we updated therapeutic targets undergoing preclinical and clinical evaluation for various cancer types. More importantly, we provided comprehensive elaboration of high throughput CRISPR-Cas9 screening in deciphering potential mechanisms of unresponsiveness to molecularly targeted therapies, which will shed light on the discovery of novel opportunities for designing next-generation anti-cancer drugs.