The Concept of Synthetic Lethality in the Context of Anticancer Therapy

Nat Rev Cancer. 2005 Sep;5(9):689-98. doi: 10.1038/nrc1691.

Abstract

Two genes are synthetic lethal if mutation of either alone is compatible with viability but mutation of both leads to death. So, targeting a gene that is synthetic lethal to a cancer-relevant mutation should kill only cancer cells and spare normal cells. Synthetic lethality therefore provides a conceptual framework for the development of cancer-specific cytotoxic agents. This paradigm has not been exploited in the past because there were no robust methods for systematically identifying synthetic lethal genes. This is changing as a result of the increased availability of chemical and genetic tools for perturbing gene function in somatic cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Genes, Lethal*
  • Humans
  • Models, Genetic*
  • Neoplasms / drug therapy*
  • Neoplasms / genetics*

Substances

  • Antineoplastic Agents