title: Synthetic lethality-based targets for discovery of new cancer therapeutics.
abstract: Synthetic lethality is based on the incompatibility of cell survival with the loss of function of two or more genes, not with loss of function of a single gene. If targets of synthetic lethality are deregulated or mutated in cancer cells, the strategy of synthetic lethality can result in significant increase of therapeutic efficacy and a favourable therapeutic window. In this review, we discuss synthetic lethality based on deficient DNA repair mechanisms, activating mutations of RAS, loss of function mutations of the tumor suppressor genes p53, Rb and von Hippel-Lindau, and disruption of interactive protein kinase networks in the context of development of new anticancer agents.
authors: Roche Diagnostics, Division Pharma, Penzberg, Germany. ulrich.weidle@roche.com
authors: Ulrich H
authors: UH
authors: Weidle
authors: Daniela
authors: D
authors: Maisel
authors: Dirk
authors: D
authors: Eick
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D004260:DNA Repair / Q000235:genetics; D015195:Drug Design; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D016259:Genes, myc; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D000068877:Imatinib Mesylate; D009154:Mutation; D010879:Piperazines / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000187:drug effects / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D016160:Retinoblastoma Protein / Q000235:genetics; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D016160:Retinoblastoma Protein; D000068877:Imatinib Mesylate; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D011065:Poly(ADP-ribose) Polymerases; D011494:Protein Kinases; C497446:VHL protein, human