Potential of the Synthetic Lethality Principle

Elucidating the first principles of synthetic lethality in cancer, including biological context, will assist clinical translation. Most cancer mutations, including those causing a loss of function, are not directly “druggable” with conventional small-molecule drugs or biologicals, such as antibodies...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2013-11, Vol.342 (6160), p.809-811
Main Authors: Nijman, Sebastian M. B., Friend, Stephen H.
Format: Article
Language:English
Subjects:
Antibodies
Cancer
Cell lines
Drug interactions
Drugs
Genes
Genetic mutation
Genetics
Lethality
Medical treatment
Mutation
Mutations
Oncology
PERSPECTIVES
Progressions
Social interaction
Topology
Translating
Tumors
Yeasts
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Summary:Elucidating the first principles of synthetic lethality in cancer, including biological context, will assist clinical translation. Most cancer mutations, including those causing a loss of function, are not directly “druggable” with conventional small-molecule drugs or biologicals, such as antibodies. Thus, despite our growing knowledge of mutations that drive cancer progression, there remains a frustrating gap in translating this information into the development of targeted treatments that kill only cancer cells. An approach that exploits a concept from genetics called “synthetic lethality” could provide a solution. But it has been over 15 years since that framework was proposed ( 1 ). Does the synthetic lethality principle still have the potential for treating cancer?
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1244669