Methodological approaches in application of synthetic lethality screening towards anticancer therapy

Br J Cancer. 2009 Apr 21;100(8):1213-8. doi: 10.1038/sj.bjc.6605000. Epub 2009 Mar 24.


A promising direction in the development of selective less toxic cancer drugs is the usage of synthetic lethality concept. The availability of large-scale synthetic low-molecular-weight chemical libraries has allowed HTS for compounds synergistic lethal with defined human cancer aberrations in activated oncogenes or tumour suppressor genes. The search for synthetic lethal chemicals in human/mouse tumour cells is greatly aided by a prior knowledge of relevant signalling and DNA repair pathways, allowing for educated guesses on the preferred potential therapeutic targets. The recent generation of human/rodents genome-wide siRNAs, and shRNA-expressing libraries, should further advance this more focused approach to cancer drug discovery.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity*
  • Drug Screening Assays, Antitumor / methods*
  • Genome
  • Genome, Human
  • Humans
  • Lethal Dose 50
  • Mammals
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / mortality
  • Oncogenes / drug effects
  • RNA, Small Interfering / genetics
  • Rodentia
  • Yeasts / drug effects
  • Yeasts / genetics


  • Antineoplastic Agents
  • RNA, Small Interfering