title: Exploiting synthetic lethal interactions for targeted cancer therapy.
abstract: Emerging data suggests that synthetic lethal interactions between mutated oncogenes/tumor suppressor genes and molecules involved in DNA damage signaling and repair can be therapeutically exploited to preferentially kill tumor cells. In this review, we discuss the concept of synthetic lethality, and describe several recent examples in which this concept was successfully implemented to target tumor cells in culture, in mouse models, and in human cancer patients.
authors.affiliation: The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: H Christian
authors.initials: HC
authors.lastname: Reinhardt
authors.forename: Hai
authors.initials: H
authors.lastname: Jiang
authors.forename: Michael T
authors.initials: MT
authors.lastname: Hemann
authors.forename: Michael B
authors.initials: MB
authors.lastname: Yaffe
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D019313:BRCA1 Protein / Q000378:metabolism; D024682:BRCA2 Protein / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D009857:Oncogenes / Q000235:genetics*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D011065:Poly(ADP-ribose) Polymerases; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases