Synthetic Lethal Networks for Precision Oncology: Promises and Pitfalls

J Mol Biol. 2018 Sep 14;430(18 Pt A):2900-2912. doi: 10.1016/j.jmb.2018.06.026. Epub 2018 Jun 20.


Synthetic lethal interactions, in which the simultaneous loss of function of two genes produces a lethal phenotype, are being explored as a means to therapeutically exploit cancer-specific vulnerabilities and expand the scope of precision oncology. Currently, three Food and Drug Administration-approved drugs work by targeting the synthetic lethal interaction between BRCA1/2 and PARP. This review examines additional efforts to discover networks of synthetic lethal interactions and discusses both challenges and opportunities regarding the translation of new synthetic lethal interactions into the clinic.

Keywords: cancer genomics; genetic interaction; precision medicine; synthetic lethal; systems biology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor
  • Computational Biology / methods
  • Disease Susceptibility
  • Epistasis, Genetic
  • Genomics / methods
  • Humans
  • Neoplasms / diagnosis
  • Neoplasms / etiology*
  • Neoplasms / metabolism
  • Neoplasms / therapy
  • Precision Medicine* / methods
  • Synthetic Lethal Mutations*
  • Translational Medical Research


  • Biomarkers, Tumor