Methodological approaches in application of synthetic lethality screening towards anticancer therapy.

Abstract

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.

• Authors: D Canaani
• Journal: British journal of cancer (Br J Cancer) Vol. 100 Issue 8 Pg. 1213-8 (Apr 21 2009) ISSN: 1532-1827 [Electronic] England
• PMID: 19319136 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antineoplastic Agents
• RNA, Small Interfering

Topics

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