BRCA1/P53: Two strengths in cancer chemoprevention

Biochim Biophys Acta Rev Cancer. 2020 Jan;1873(1):188339. doi: 10.1016/j.bbcan.2020.188339. Epub 2020 Jan 7.

Abstract

Increasing emphasis has been given to prevention as a feasible approach to reduce the cancer burden. However, for its clinical success, further advances are required to identify effective chemopreventive agents. This review affords a critical and up-to-date discussion of issues related to cancer prevention, including an in-depth knowledge on BRCA1 and p53 tumor suppressor proteins as key molecular players. Indeed, it compiles the most recent advances on the topic, highlighting the unique potential of BRCA1 and p53 germline mutations as molecular biomarkers for risk assessment and targets for chemoprevention. Relevant evidences are herein provided supporting the effectiveness of distinct pharmacological agents in cancer prevention, by targeting BRCA1 and p53. Moreover, the rationale for using germline mutant BRCA1- or p53-related cancer syndromes as model systems to investigate effective chemopreventive agents is also addressed. Altogether, this work provides an innovative conception about the dependence on p53 and BRCA1 co-inactivation in tumor formation and development, emphasizing the relationship between these two proteins as an encouraging direction for future personalized pharmacological interventions in cancer prevention.

Keywords: BRCA1; Cancer risk; Chemopreventive agents; Hereditary breast and ovarian cancer syndrome; Li-Fraumeni syndrome; p53.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • BRCA1 Protein / genetics*
  • BRCA1 Protein / metabolism
  • Chemoprevention / methods*
  • Female
  • Germ-Line Mutation*
  • Humans
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / prevention & control*
  • Selective Estrogen Receptor Modulators / therapeutic use
  • Tamoxifen / therapeutic use*
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • Selective Estrogen Receptor Modulators
  • Tumor Suppressor Protein p53
  • Tamoxifen