Synthetic lethal approaches to breast cancer therapy

Nat Rev Clin Oncol. 2010 Dec;7(12):718-24. doi: 10.1038/nrclinonc.2010.172. Epub 2010 Oct 19.

Abstract

The promise of personalized therapy for breast cancer is that therapeutic efficacy will be increased while toxic effects are reduced to a minimum. To achieve this goal, there is now an emphasis on the design of therapies that are based not only on the clinical manifestations of the disease, but also on the underlying molecular and cellular biology of cancer. However, identifying targets for personalized therapies in breast cancer is challenging. Here, we describe how biological concepts such as synthetic lethality and oncogene addiction can be used to identify new therapeutic targets and approaches. We discuss the current clinical developments in implementing synthetic lethality therapies, and highlight new ways in which this approach could be used to target specific subsets of breast cancer.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • BRCA1 Protein / deficiency
  • BRCA1 Protein / physiology
  • BRCA2 Protein / deficiency
  • BRCA2 Protein / physiology
  • Biomarkers, Tumor
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Case Management
  • Clinical Trials as Topic / statistics & numerical data
  • DNA Repair / drug effects
  • DNA Repair / genetics
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Genes, BRCA1
  • Genes, BRCA2
  • Humans
  • Male
  • Molecular Targeted Therapy*
  • Multicenter Studies as Topic / statistics & numerical data
  • Mutation
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / genetics
  • Oncogenes*
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics
  • Phthalazines / pharmacology
  • Phthalazines / therapeutic use
  • Piperazines / pharmacology
  • Piperazines / therapeutic use
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Precision Medicine / trends*
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / genetics
  • RNA Interference

Substances

  • Antineoplastic Agents
  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Biomarkers, Tumor
  • Enzyme Inhibitors
  • Neoplasm Proteins
  • Phthalazines
  • Piperazines
  • Poly(ADP-ribose) Polymerase Inhibitors
  • olaparib