Exploring the genetic space of the DNA damage response for cancer therapy through CRISPR‐based screens
The concepts of synthetic lethality and viability have emerged as powerful approaches to identify vulnerabilities and resistances within the DNA damage response for the treatment of cancer. Historically, interactions between two genes have had a longstanding presence in genetics and have been identi...
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Published in | Molecular oncology Vol. 16; no. 21; pp. 3778 - 3791 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
United States
John Wiley & Sons, Inc
01.11.2022
John Wiley and Sons Inc Wiley |
Subjects | |
Online Access | Get full text |
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Summary: | The concepts of synthetic lethality and viability have emerged as powerful approaches to identify vulnerabilities and resistances within the DNA damage response for the treatment of cancer. Historically, interactions between two genes have had a longstanding presence in genetics and have been identified through forward genetic screens that rely on the molecular basis of the characterized phenotypes, typically caused by mutations in single genes. While such complex genetic interactions between genes have been studied extensively in model organisms, they have only recently been prioritized as therapeutic strategies due to technological advancements in genetic screens. Here, we discuss synthetic lethal and viable interactions within the DNA damage response and present how CRISPR‐based genetic screens and chemical compounds have allowed for the systematic identification and targeting of such interactions for the treatment of cancer.
The combination of CRISPR gene editing and drug treatments in a pooled screening format allows for the discovery of novel gene‐drug interactions. These interactions can potentially provide biomarkers for drug sensitivity and resistance in a clinical setting. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23 |
ISSN: | 1574-7891 1878-0261 1878-0261 |
DOI: | 10.1002/1878-0261.13272 |