Using Synthetic Lethality in the Targeted Treatment of Human Cancers


Authors: Matthew J. Imrie, Alexandria Jack, and Francis Choy
Page Range: 223-234
Published in: Journal of Biochemistry and Molecular Biology in the Post Genomic Era, 1#2 (2011)
ISSN: 2156-5732

Table of Contents


Chemotherapeutics are globally accepted drugs for treating cancerous malignancies. The discovery of new anti-cancer drugs is generally not dependent on the genetic context of gene interactions within the cell. Additionally, chemotherapeutics have negative effects on non-cancerous cells. Gene dosage can be used as a basis to explain the concepts of oncogene addiction (the apparent dependency of cancers on one or a few genes for the expression and maintenance of the malignant phenotype) and synthetic lethality. Two genes are said to be synthetically lethal if a deleterious mutation in both genes results in cell death. They are said to be synthetically sick if their deletion results in severely reduced fitness. We discuss the synthetic lethality surrounding the DNA repair protein poly(ADP-ribose) polymerase and its interactions with mutations in BRCA1, BRCA2 and mTOR. We then explain how one of the hallmarks of cancer, an abundance of mutations, was used to determine potential synthetic lethal interactions in human cancers using investigations into interactions between homologous gene products from Saccharomyces cerevisiae. Large scale models such as the ones described here could have a significant impact on future investigations into potential targets for anti-cancer drug therapies.

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