From the Journals

Interplay of TP53, ESR2 may expand treatment options for some TNBCs

View on the News

Knowledge of molecular players can help personalize treatment

“The ability to selectively administer endocrine therapy should, in principle, lead to greater response rates,” according to an editorial by Sunil Badve, MBBS, FRCPath, and Yesim Gokmen-Polar, PhD (J Natl Cancer Inst. 2019 Apr 16. doi: 10.1093/jnci/djz052).

The study illustrates that “company matters” when it comes to the impact of markers and mutations in cancers, they maintain. “The intracellular environment is a complex milieu wherein changes in one player can have a dramatic impact on DNA, RNA and protein interactions. The players in the neighborhood could further affect cellular phenotype.

“Acknowledging these processes also provides a reality check for those of us involved in precision medicine, wherein treatments are being prescribed based on the presence of single gene mutations ... ” Dr. Badve and Dr. Gokmen-Polar noted. “The cooperativity and interactions of cellular networks may, to a large extent, determine the prognostic and predictive utility of mutations in patients.”

The new study “is a good step in this direction and provides compelling reasons to understand the combinatorial impact to determine clinically actionable strategies and solutions,” they concluded.

Dr. Badve and Dr. Gokmen-Polar are in the department of pathology and laboratory medicine at Indiana University, Indianapolis.



“These findings suggest that ESR2-TP53 combination can be used to stratify TNBC into therapeutically actionable subgroups,” Dr. Das and coinvestigators proposed.

“Our data that treatment with tamoxifen can lead to sequestration of mutant TP53 away from TP73 and thereby reactivate tumor suppressor activities of TP73, provide for the first time, a strong rationale for suggesting that tamoxifen therapy could be beneficial to basal-type/TNBC patients expressing mutant TP53,” they concluded. “On the other hand, based on our data that ESR2 is proproliferative in the WT [wild-type] TP53 context, we predict that in TNBCs expressing WT TP53, tamoxifen or other agents that increase ESR2-WTP53 interaction may not only be ineffective as antitumor agents, but also may contribute to adverse outcome.”

The authors disclosed that they had no conflicts of interest. The study was supported by the several sources including the National Cancer Institute and Susan G. Komen for the Cure.

SOURCE: Mukhopadhyay UK et al. J Natl Cancer Inst. 2019 Apr 16. doi: 10.1093/jnci/djz051.


Next Article: