“When combined, these therapeutic agents can hijack signals that occur naturally in the body to eliminate breast cells after lactation stops in order to kill these aggressive cancer cells,” said lead author Karen Cichowski. , PhD, of the Division of Genetics at Brigham and Women’s. Hospital (BWH). “Our results provide compelling support for the development of clinical trials to test whether the combination of these agents could benefit patients with TNBC.”

Specifically, the researchers found that by combining two types of agents called EZH2 and AKT inhibitors, they could induce TNBC cells to differentiate. Once the cells differentiate, these agents kill tumor cells by triggering a process similar to involution, which normally occurs when breast tissue returns to a non-lactating state after a mother stops producing breast milk. Researchers also used machine learning to predict patient responses – another step that could help set the stage for clinical trials in patients.

In future studies, researchers want to determine whether similar drug combinations might be effective in other tumor types.

Paternity: Besides Cichowski, BWH authors include Amy E Schade, Naiara Perurena, Yoona Yang, Carrie L Rodriguez, Anjana Krishnan, Alycia Gardner, Patrick Loi, Yilin Xu, Van TM Nguyen, GM Mastellone, Natalie F Pilla, Marina Watanabe, Keiichi Ota . , Rachel A Davis, Kaia Mattioli, Dongxi Xiang, Zhe Li and Sandro Santagata.

Disclosures: Cichowski is an advisor to Genentech and serves on the scientific advisory board of Erasca, Inc. Disclosures from other authors can be found within the article.

Funding: This work was supported by a Cancer Research UK Grand Challenge and Mark Foundation for Cancer Research grant to the SPECIFICANCER (KC) team and by a DOD BC201085P1 Transformative Breast Cancer Consortium award.