Synthetic Lethality in Cancer Therapeutics: The Next Generation.
Journal
Cancer discovery
ISSN: 2159-8290
Titre abrégé: Cancer Discov
Pays: United States
ID NLM: 101561693
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
16
10
2020
revised:
01
01
2021
accepted:
23
02
2021
pubmed:
3
4
2021
medline:
1
3
2022
entrez:
2
4
2021
Statut:
ppublish
Résumé
Synthetic lethality (SL) provides a conceptual framework for tackling targets that are not classically "druggable," including loss-of-function mutations in tumor suppressor genes required for carcinogenesis. Recent technological advances have led to an inflection point in our understanding of genetic interaction networks and ability to identify a wide array of novel SL drug targets. Here, we review concepts and lessons emerging from first-generation trials aimed at testing SL drugs, discuss how the nature of the targeted lesion can influence therapeutic outcomes, and highlight the need to develop clinical biomarkers distinct from those based on the paradigms developed to target activated oncogenes. SIGNIFICANCE: SL offers an approach for the targeting of loss of function of tumor suppressor and DNA repair genes, as well as of amplification and/or overexpression of genes that cannot be targeted directly. A next generation of tumor-specific alterations targetable through SL has emerged from high-throughput CRISPR technology, heralding not only new opportunities for drug development, but also important challenges in the development of optimal predictive biomarkers.
Identifiants
pubmed: 33795234
pii: 2159-8290.CD-20-1503
doi: 10.1158/2159-8290.CD-20-1503
pmc: PMC8295179
mid: NIHMS1680455
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1626-1635Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA247749
Pays : United States
Informations de copyright
©2021 American Association for Cancer Research.
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