Olaparib for the treatment of breast cancer

Expert Opin Investig Drugs. 2017 Jun;26(6):751-759. doi: 10.1080/13543784.2017.1318847. Epub 2017 Apr 21.

Abstract

Basal-like breast cancer is characterized by being triple negative and aggressive. Defects in DNA repair is a promising therapeutic target as BRCA alterations are found in 11 to 42% of these tumors, with a frequency varying according to family history and ethnicity. The oral PARP inhibitors exploit this deficiency through a synthetic lethality and are considered as promising anticancer therapies, especially in patients harboring BRCA1 or BRCA 2 mutations. Areas covered: Olaparib is one of the most widely investigated PARP inhibitors. Here, the preclinical data, completed clinical trials and ongoing investigations are discussed. Expert opinion: PARP inhibitors show promising results in breast cancer. However, several issues are raised including the identification of biomarkers to predict treatment response and strategies to counteract emerging resistance. Moreover, the results from ongoing phase III trials of olaparib in breast cancer are still awaited.

Keywords: BRCA1/2; BRCAness; Breast cancer; PARP inhibitors; olaparib.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Mutation
  • Phthalazines / pharmacology
  • Phthalazines / therapeutic use*
  • Piperazines / pharmacology
  • Piperazines / therapeutic use*
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use

Substances

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