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. Our results provide compelling support for the development of clinical trials to test whether combining these agents could benefit patients with TNBC."
Karen Cichowski, PhD, senior author, Division of Genetics, Brigham and Women's Hospital (BWH)
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.
Source:
Journal reference:
Schade, A. E., et al. (2024) AKT and EZH2 inhibitors kill TNBCs by hijacking mechanisms of involution. Nature. doi.org/10.1038/s41586-024-08031-6.
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