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

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, unr...

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Detalles Bibliográficos
Autores principales: Hou, Jue, He, Zongsheng, Liu, Tian, Chen, Dongfeng, Wang, Bin, Wen, Qinglian, Zheng, Xi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8970599/
https://www.ncbi.nlm.nih.gov/pubmed/35372044
http://dx.doi.org/10.3389/fonc.2022.755053
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author Hou, Jue
He, Zongsheng
Liu, Tian
Chen, Dongfeng
Wang, Bin
Wen, Qinglian
Zheng, Xi
author_facet Hou, Jue
He, Zongsheng
Liu, Tian
Chen, Dongfeng
Wang, Bin
Wen, Qinglian
Zheng, Xi
author_sort Hou, Jue
collection PubMed
description 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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spelling pubmed-89705992022-04-01 Evolution of Molecular Targeted Cancer Therapy: Mechanisms of Drug Resistance and Novel Opportunities Identified by CRISPR-Cas9 Screening Hou, Jue He, Zongsheng Liu, Tian Chen, Dongfeng Wang, Bin Wen, Qinglian Zheng, Xi Front Oncol Oncology 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. Frontiers Media S.A. 2022-03-17 /pmc/articles/PMC8970599/ /pubmed/35372044 http://dx.doi.org/10.3389/fonc.2022.755053 Text en Copyright © 2022 Hou, He, Liu, Chen, Wang, Wen and Zheng https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Hou, Jue
He, Zongsheng
Liu, Tian
Chen, Dongfeng
Wang, Bin
Wen, Qinglian
Zheng, Xi
Evolution of Molecular Targeted Cancer Therapy: Mechanisms of Drug Resistance and Novel Opportunities Identified by CRISPR-Cas9 Screening
title Evolution of Molecular Targeted Cancer Therapy: Mechanisms of Drug Resistance and Novel Opportunities Identified by CRISPR-Cas9 Screening
title_full Evolution of Molecular Targeted Cancer Therapy: Mechanisms of Drug Resistance and Novel Opportunities Identified by CRISPR-Cas9 Screening
title_fullStr Evolution of Molecular Targeted Cancer Therapy: Mechanisms of Drug Resistance and Novel Opportunities Identified by CRISPR-Cas9 Screening
title_full_unstemmed Evolution of Molecular Targeted Cancer Therapy: Mechanisms of Drug Resistance and Novel Opportunities Identified by CRISPR-Cas9 Screening
title_short Evolution of Molecular Targeted Cancer Therapy: Mechanisms of Drug Resistance and Novel Opportunities Identified by CRISPR-Cas9 Screening
title_sort evolution of molecular targeted cancer therapy: mechanisms of drug resistance and novel opportunities identified by crispr-cas9 screening
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8970599/
https://www.ncbi.nlm.nih.gov/pubmed/35372044
http://dx.doi.org/10.3389/fonc.2022.755053
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