Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Dec;55(12):2039-2048.
doi: 10.1038/s41588-023-01557-x. Epub 2023 Nov 30.

Complex synthetic lethality in cancer

Colm J Ryan  1 , Lovely Paul Solomon Devakumar  2 , Stephen J Pettitt  3 , Christopher J Lord  4
Affiliations
Review

Complex synthetic lethality in cancer

Colm J Ryan et al. Nat Genet. 2023 Dec.

Abstract

The concept of synthetic lethality has been widely applied to identify therapeutic targets in cancer, with varying degrees of success. The standard approach normally involves identifying genetic interactions between two genes, a driver and a target. In reality, however, most cancer synthetic lethal effects are likely complex and also polygenic, being influenced by the environment in addition to involving contributions from multiple genes. By acknowledging and delineating this complexity, we describe in this article how the success rate in cancer drug discovery and development could be improved.

PubMed Disclaimer

References

    1. Ryan, C. J., Bajrami, I. & Lord, C. J. Synthetic lethality and cancer—penetrance as the major barrier. Trends Cancer 4, 671–683 (2018). - PubMed - DOI
    1. Fisher, R. A. The correlation between relatives on the supposition of Mendelian inheritance. Trans. R. Soc. Edinb. 52, 399–433 (1919). - DOI
    1. Kaelin, W. G. Jr. The concept of synthetic lethality in the context of anticancer therapy. Nat. Rev. Cancer 5, 689–698 (2005). - PubMed - DOI
    1. Lord, C. J. & Ashworth, A. PARP inhibitors: synthetic lethality in the clinic. Science 355, 1152–1158 (2017). - PubMed - PMC - DOI
    1. Behan, F. M. et al. Prioritization of cancer therapeutic targets using CRISPR–Cas9 screens. Nature 568, 511–516 (2019). - PubMed - DOI

MeSH terms

Substances

LinkOut - more resources