title: [Synthetic lethality as a new concept for the treatment of cancer].
abstract: Following DNA damage, cells activate a complex DNA-damage-response (DDR) signaling network to arrest the cell cycle, repair DNA and, if the extend of damage is beyond repair capacity, induce apoptosis. DDR genes are among the most commonly mutated genes in human cancer and it is believed that these lesions promote a "MUTATOR-PHENOTYPE" that fuels the runaway proliferation of cancer cells. However, these genetic lesions can also be seen as the "Achilles heel" of cancer. These tumor cell-specific vulnerabilities are of extraordinary clinical interest, since they allow genetically-guided novel therapeutic regimens for the treatment of cancer. Here, we discuss such a novel therapeutic concept - synthetic lethality. We focus on the first successful clinical applications of synthetic lethality for the treatment of different cancer entities. In addition, we give a brief review of recently developed, synthetic lethality-based approaches that are close to clinical testing.
authors.affiliation: Medizinische Klinik I, Universitätsklinik Köln.
authors.forename: G S
authors.initials: GS
authors.lastname: Herter-Sprie
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.forename: K
authors.initials: K
authors.lastname: Höpker
authors.forename: H C
authors.initials: HC
authors.lastname: Reinhardt
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D004252:DNA Mutational Analysis; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D004843:Epistasis, Genetic / Q000187:drug effects / Q000235:genetics; D005260:Female; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D009857:Oncogenes / Q000187:drug effects / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics; D010641:Phenotype; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases