A CRISPR Path to Finding Vulnerabilities and Solving Drug Resistance: Targeting the Diverse Cancer Landscape and Its Ecosystem

Autor: Benjamin McLean, Aji Istadi, Teleri Clack, Mezzalina Vankan, Daniel Schramek, G. Gregory Neely, Marina Pajic
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Advanced Genetics, Vol 3, Iss 4, Pp n/a-n/a (2022)
Druh dokumentu: article
ISSN: 2641-6573
DOI: 10.1002/ggn2.202200014
Popis: Abstract Cancer is the second leading cause of death globally, with therapeutic resistance being a major cause of treatment failure in the clinic. The dynamic signaling that occurs between tumor cells and the diverse cells of the surrounding tumor microenvironment actively promotes disease progression and therapeutic resistance. Improving the understanding of how tumors evolve following therapy and the molecular mechanisms underpinning de novo or acquired resistance is thus critical for the identification of new targets and for the subsequent development of more effective combination regimens. Simultaneously targeting multiple hallmark capabilities of cancer to circumvent adaptive or evasive resistance may lead to significantly improved treatment response in the clinic. Here, the latest applications of functional genomics tools, such as clustered regularly interspaced short palindromic repeats (CRISPR) editing, to characterize the dynamic cancer resistance mechanisms, from improving the understanding of resistance to classical chemotherapeutics, to deciphering unique mechanisms that regulate tumor responses to new targeted agents and immunotherapies, are discussed. Potential avenues of future research in combating therapeutic resistance, the contribution of tumor–stroma signaling in this setting, and how advanced functional genomics tools can help streamline the identification of key molecular determinants of drug response are explored.
Databáze: Directory of Open Access Journals
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