Building high-resolution synthetic lethal networks: a 'Google map' of the cancer cell

Trends Mol Med. 2014 Dec;20(12):704-15. doi: 10.1016/j.molmed.2014.09.009. Epub 2014 Oct 22.

Abstract

The most commonly used therapies for cancer involve delivering high doses of radiation or toxic chemicals to the patient that also cause substantial damage to normal tissue. To overcome this, researchers have recently resorted to a basic biological concept called 'synthetic lethality' (SL) that takes advantage of interactions between gene pairs. The identification of SL interactions is of considerable therapeutic interest because if a particular gene is SL with a tumor-causing mutation, then the targeting that gene carries therapeutic advantages. Mapping these interactions in the context of human cancer cells could hold the key to effective, targeted cancer treatments. In this review, we cover the recent advances that aim to identify these SL interactions using unbiased genetic screens.

Keywords: high resolution phenotypic interactions; negative genetic interaction; pooled shRNA and sgRNA screening; synthetic dosage lethality; synthetic lethality.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Line, Tumor
  • Chromosome Mapping
  • Clustered Regularly Interspaced Short Palindromic Repeats / genetics*
  • Genetic Association Studies
  • Genetic Testing
  • Genetic Therapy
  • Humans
  • Models, Genetic
  • Multigene Family
  • Mutation
  • Neoplasms / genetics*
  • Neoplasms / therapy
  • RNA Interference
  • Systems Biology / methods*