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Complex synthetic lethality in cancer
Nature Genetics, 2023The 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 ...
Colm J. Ryan +3 more
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Synthetic lethality and cancer
Nature Reviews Genetics, 2017A synthetic lethal interaction occurs between two genes when the perturbation of either gene alone is viable but the perturbation of both genes simultaneously results in the loss of viability. Key to exploiting synthetic lethality in cancer treatment are the identification and the mechanistic characterization of robust synthetic lethal genetic ...
Nigel J O'Neil +2 more
exaly +3 more sources
2005
The synthetic lethal screen is a method of isolating novel mutants whose survival is dependent on a gene of interest. Combining the colony-color assay with a synthetic lethal screen offers a means to visually detect a mutant that depends on a plasmid for survival. Screening for synthetic lethals can be achieved in four steps.
Leslie, Barbour, Wei, Xiao
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The synthetic lethal screen is a method of isolating novel mutants whose survival is dependent on a gene of interest. Combining the colony-color assay with a synthetic lethal screen offers a means to visually detect a mutant that depends on a plasmid for survival. Screening for synthetic lethals can be achieved in four steps.
Leslie, Barbour, Wei, Xiao
openaire +2 more sources
Searching for synthetic lethality in cancer
Current Opinion in Genetics & Development, 2011The incentive to develop personalised therapy for cancer treatment is driven by the premise that it will increase therapeutic efficacy and reduce toxicity. Understanding the underlying cellular and molecular basis of the disease has been extremely important in the design of these novel therapies; however, identifying new drug targets for personalised ...
Rachel, Brough +4 more
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2002
Publisher Summary Identification of proteins that interact to perform a common function is crucial to understanding the mechanisms of cellular processes. Both genetic and biochemical methods are used to uncover an interaction between two proteins. In yeast, many genetic screens have been developed, which begin with the mutation of a gene of interest ...
Vivien, Measday, Philip, Hieter
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Publisher Summary Identification of proteins that interact to perform a common function is crucial to understanding the mechanisms of cellular processes. Both genetic and biochemical methods are used to uncover an interaction between two proteins. In yeast, many genetic screens have been developed, which begin with the mutation of a gene of interest ...
Vivien, Measday, Philip, Hieter
openaire +2 more sources
Synthetic lethality and beyond
Science Translational Medicine, 2016DNA damage–induced binding of DNA methyltransferases maximizes the efficacy of poly(ADP-ribose) polymerase inhibitors.
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Synthetic Lethality in Cancer Therapeutics [PDF]
Annual Review of Cancer Biology, 2017 Treatment with targeted drugs has primarily focused on the genes and pathways that are mutated in cancer, which severely limits the repertoire of drug targets. Synthetic lethality exploits the notion that the presence of a mutation in a cancer gene is often associated with a new vulnerability that can be targeted therapeutically, thus greatly ...
Roderick L Beijersbergen +2 more
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Synthetic Lethal Interactions in Cancer Therapy
Current Cancer Drug Targets, 2016Silencing of two or more complementary signaling pathways can lead to cell death, while loss of any single genetic function does not show a severe phnotype, this kind of inter action is coined as "synthetic lethality". Nowadays, synthetic lethality has become a widely used anti-cancer strategy.We reviewed the synthetic lethal interactions exploited in ...
Xinwei, Geng +3 more
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Collateral lethality: A unique type of synthetic lethality in cancers
Pharmacology & TherapeuticsGenetic interactions play crucial roles in cell-essential functions. Intrinsic genetic defects in tumors typically involve gain-of- and loss-of-function mutations in tumor suppressor genes (TSGs) and oncogenes, respectively, providing potential antitumor vulnerabilities.
Zichen, Zhao +4 more
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