Exploiting synthetic lethal interactions for targeted cancer therapy

Cell Cycle. 2009 Oct 1;8(19):3112-9. doi: 10.4161/cc.8.19.9626.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Ataxia Telangiectasia Mutated Proteins
  • BRCA1 Protein / metabolism
  • BRCA2 Protein / metabolism
  • Cell Cycle Proteins / metabolism
  • DNA Damage
  • DNA Repair
  • DNA-Binding Proteins / metabolism
  • Humans
  • Mice
  • Neoplasms / genetics
  • Neoplasms / therapy*
  • Oncogenes / genetics*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Proteins / metabolism

Substances

  • BRCA1 Protein
  • BRCA2 Protein
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Poly(ADP-ribose) Polymerases
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Atm protein, mouse
  • Protein-Serine-Threonine Kinases