Journal
FRONTIERS IN ONCOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2022.755053
Keywords
molecular targeted therapy; drug resistance; CRISPR-Cas9 screening; patient-derived xenograft (PDX); patient-derived organoid
Categories
Funding
- National Natural Science Foundation of China (NSFC) [81822032, 91959111, 81872027]
- Natural Science Foundation of Chongqing [CSTC2019JCYJJQX0027, cstc2021jcyj-msxmX0405]
- Health Commission of Sichuan Province [17PJ575]
- Office of Science and Technology and Talent Work of Luzhou [2017LZXNYD-Z01]
- Army Medical University [2019CXLCA001, 2018XLC2023, 2019XQY19]
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Molecular targeted therapy has significantly improved cancer treatment by providing better therapeutic responses and reducing systemic toxicity. However, therapeutic resistance remains a major challenge, hindering the continuous clinical benefits for cancer patients. The recent development of advanced technologies, such as CRISPR-Cas9 screening and patient-derived models, has provided powerful tools to understand the underlying mechanisms of resistance in targeted cancer therapies. This review explores therapeutic targets and the high-throughput CRISPR-Cas9 screening technology, which can uncover potential mechanisms of unresponsiveness and guide the development of next-generation anti-cancer drugs.
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.
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