Mutant p53 in breast cancer: potential as a therapeutic target and biomarker

  • Michael J. Duffy
  • Naoise C. Synnott
  • John Crown
Review

Abstract

Objective

The aim of this article is to discuss mutant p53 as a possible therapeutic target and biomarker for breast cancer.

Results

TP53 (p53) is the most frequently mutated gene in invasive breast cancer. Although mutated in 30–35% of all cases, p53 is mutated in approximately 80% of triple-negative (TN) tumors (i.e., tumors negative for ER, PR, and HER2). Because of this high prevalence, mutated p53 is both a potential biomarker and therapeutic target for patients with breast cancer, especially for those with the TN subtype. Although several retrospective studies have investigated a potential prognostic and therapy predictive role for mutant p53 in breast cancer, the results to date are mixed. Thus, at present, mutant p53 cannot be recommended as a prognostic or therapy predictive biomarker in breast cancer. In contrast to the multiple reports on a potential biomarker role, few studies had until recently, investigated mutant p53 as a potential target for breast cancer treatment. In the last decade, however, several compounds have become available which can reactivate mutant p53 protein and convert it to a conformation with wild-type properties. Some of these compounds, especially PRIMA-1, APR-246 PK11007, and COTI-2, have been found to exhibit anticancer activity in preclinical models of breast cancer.

Conclusion

Since p53 is mutated in the vast majority of TN breast cancers, compounds such as APR-246, PK11007, and COTI-2 are potential treatments for patients with this subform of the disease. Further research is necessary to identify a potential biomarker role for mutant p53 in breast cancer.

Keywords

p53 Breast cancer Triple-negative Biomarker Therapeutic target APR-246 

Notes

Acknowledgements

The authors wish to thank the Science Foundation Ireland; the Strategic Research Cluster Award (08/SRC/B1410) to Molecular Therapeutics for Cancer Ireland; the Clinical Cancer Research Trust and the Irish Cancer Society Collaborative Cancer Research Centre BREAST-PREDICT programme (CCRC13GAL); and the Health Research Board Clinician Scientist Award (CSA/2007/11).

Disclosures

None.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Michael J. Duffy
    • 1
    • 2
  • Naoise C. Synnott
    • 2
  • John Crown
    • 3
  1. 1.UCD Clinical Research CentreSt. Vincent’s University HospitalDublin 4Ireland
  2. 2.UCD School of Medicine, Conway Institute of Biomolecular and Biomedical ResearchUniversity College DublinDublinIreland
  3. 3.Department of Medical OncologySt. Vincent’s University HospitalDublinIreland

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