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

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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.

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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).

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Duffy, M.J., Synnott, N.C. & Crown, J. Mutant p53 in breast cancer: potential as a therapeutic target and biomarker. Breast Cancer Res Treat 170, 213–219 (2018). https://doi.org/10.1007/s10549-018-4753-7

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