title: Application of the concept synthetic lethality toward anticancer therapy: a promise fulfilled?
abstract: Back in 1997, a suggestion to apply the concept of synthetic lethality towards the development of selective, less toxic, cancer drugs and anticancer targets, was brought forward. The availability of large scale synthetic, low-molecular-weight chemical libraries seemed to lend itself to the concept. Human/mouse genome-wide siRNAs and shRNA-expressing libraries allowing high throughput screening for target genes synergistic lethal with defined human cancer aberrations, also raised high hopes of a soon to be established selective therapy. Sixteen years later, the major experimental aspects relating to the implementation of this more focused approach to cancer drug discovery, is briefly and critically reviewed.
authors: Department of Biochemistry and Molecular Biology, Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel. Electronic address: canaani@post.tau.ac.il.
authors: Dan
authors: D
authors: Canaani
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D055808:Drug Discovery / Q000639:trends*; D006801:Humans; D009154:Mutation / Q000187:drug effects; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D034741:RNA, Small Interfering / Q000235:genetics / Q000627:therapeutic use; D054852:Small Molecule Libraries / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D054852:Small Molecule Libraries
keywords: Cancer therapy; Chemical synthetic lethality; Genetic synthetic lethality; Oncogenes; RNAi; Tumor suppressor genes