New therapeutic strategy identified for triple negative breast cancer

Triple negative breast cancer (TNBC) remains the most aggressive and deadly type of breast cancer, but new findings from cancer researchers at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, are pointing the way toward therapeutic strategies that could be tested in clinical trials in the future. Using patient-derived samples in pre-clinical work, researchers discovered that by combining two therapeutic agents they could nudge TNBC cells into a more treatable state. Findings are published in Nature.

“When combined, these therapeutic agents can hijack signals that occur naturally in the body to eliminate breast cells after the cessation of lactation to kill these aggressive cancer cells,” said senior 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 combining these agents could benefit patients with TNBC.”

Specifically, the researchers discovered that that by combining two types of agents known as EZH2 and AKT inhibitors, they could coax TNBC cells to differentiate. Once the cells are differentiated, 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. The 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, the researchers are interested in exploring whether similar drug combinations may be effective in other tumor types.

Authorship: In addition to 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 at Genentech and serves on the scientific advisory board of Erasca, Inc. Disclosures for other authors can be found in the paper.

Funding: Team SPECIFICANCER is funded by Cancer Research UK and The Mark Foundation for Cancer Research through Cancer Grand Challenges. This work was also supported by a DOD BC201085P1 Transformative Breast Cancer Consortium Award.

Paper cited: Schade AE et al. “AKT and EZH2 inhibitors kill TNBCs by hijacking mechanisms of involution” Nature DOI: 10.1038/s41586-024-08031-6

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About the Mark Foundation

The Mark Foundation for Cancer Research, a charitable organization based in New York City, actively partners with scientists worldwide to accelerate research that will transform cancer prevention, diagnosis, and treatment.  Since 2017, The Mark Foundation has awarded over $230 million in grants to investigators at more than 100 academic institutions across 16 countries, with research programs focusing on early career support, team science collaboration, new technology innovation, and therapeutics discovery.  Additionally, The Mark Foundation maintains a growing portfolio of investments in early-stage cancer diagnostics and therapeutics companies, including several that have transitioned from grantee projects into commercial development.  To learn more, please visit www.themarkfoundation.org.