Triple negative breast cancer (TNBC) continues to be the most aggressive and lethal form of breast cancer. However, recent discoveries by cancer researchers at Brigham and Women’s Hospital, part of the Mass General Brigham healthcare system, are paving the way for new treatment strategies that could soon be tested in clinical trials. By utilizing samples from patients in their pre-clinical research, the scientists found that combining two specific therapeutic agents can push TNBC cells into a more manageable state. These results are detailed in the journal Nature.
Triple negative breast cancer (TNBC) continues to be the most aggressive and lethal form of breast cancer. However, recent discoveries by cancer researchers at Brigham and Women’s Hospital, a part of the Mass General Brigham healthcare system, suggest potential therapeutic approaches that could be explored in future clinical trials. By working with samples from patients in their pre-clinical research, the team found that by merging two treatment agents, they could transform TNBC cells into a more manageable form. These findings have been published in Nature.
“By combining these treatment agents, we can take advantage of naturally occurring signals in the body that eliminate breast cells after lactation ends, leading to the destruction of these aggressive cancer cells,” explained senior author Karen Cichowski, PhD, from the Division of Genetics at Brigham and Women’s Hospital (BWH). “Our findings strongly support initiating clinical trials to determine if this combination could benefit patients suffering from TNBC.”
Specifically, the researchers found that using agents known as EZH2 and AKT inhibitors together could help TNBC cells to differentiate. Once these cells differentiate, the agents can eliminate tumor cells by activating a process similar to involution, the natural return of breast tissue to a non-lactating state after breastfeeding stops. The team also employed machine learning techniques to forecast how patients might respond, which is another important step that could enhance the preparation for clinical trials in patients.
Looking forward, the researchers are eager to investigate whether this drug combination approach might also be effective for other types of tumors.
Contributors: Besides Cichowski, other authors from BWH 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.
Conflicts of Interest: Cichowski serves as an advisor at Genentech and is a member of the scientific advisory board for Erasca, Inc. Additional disclosures for other authors can be found in the research paper.
Funding: This research received funding from a grant provided by the Cancer Research UK Grand Challenge and the Mark Foundation for Cancer Research to the SPECIFICANCER team (led by KC) as well as a DOD BC201085P1 Transformative Breast Cancer Consortium Award.
