Functional genomics approaches to elucidate vulnerabilities of intrinsic and acquired chemotherapy resistance

  • Drug resistance is a commonly unavoidable consequence of cancer treatment that results in therapy failure and disease relapse. Intrinsic (pre-existing) or acquired resistance mechanisms can be drug-specific or be applicable to multiple drugs, resulting in multidrug resistance. The presence of drug resistance is, however, tightly coupled to changes in cellular homeostasis, which can lead to resistance-coupled vulnerabilities. Unbiased gene perturbations through RNAi and CRISPR technologies are invaluable tools to establish genotype-to-phenotype relationships at the genome scale. Moreover, their application to cancer cell lines can uncover new vulnerabilities that are associated with resistance mechanisms. Here, we discuss targeted and unbiased RNAi and CRISPR efforts in the discovery of drug resistance mechanisms by focusing on first-in-line chemotherapy and their enforced vulnerabilities, and we present a view forward on which measures should be taken to accelerate their clinical translation.

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Author:Ronay Cetin, Eva Quandt, Manuel KaulichORCiD
Parent Title (English):Cells
Place of publication:Basel
Document Type:Article
Date of Publication (online):2021/01/28
Date of first Publication:2021/01/28
Publishing Institution:Universit├Ątsbibliothek Johann Christian Senckenberg
Release Date:2021/01/30
Tag:RNAi and CRISPR screens; cancer and drug vulnerabilities; chemotherapy resistance; functional genomics
Issue:Article 260
Page Number:27
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0