Basal-like breast cancer (BLBC) accounts for up to 80% of cases of triple-negative breast cancer—a highly aggressive type of breast cancer that disproportionately affects younger women and women of African ancestry and frequently occurs in women carrying BRCA1 germline mutations. With no targeted therapies available for treating BLBC, current treatments rely heavily on chemotherapy, which often leads to serious side effects and drug resistance. 

Recent studies have shown that BLBC occurs because certain breast cells de-differentiate into cells resembling embryonic mammary stem cells, a process driven by the key transcription factor SOX9. Wenjun Guo, Ph.D., has received a five-year, $2.7 million National Cancer Institute grant to determine the underlying mechanisms that drive the de-differentiation of breast cells that lead to BLBC. Using mouse and human breast organoid culture, Dr. Guo and colleagues will define the intermediate cell states critical for BLBC progression, determine SOX9’s role in causing breast cells to de-differentiate, and explore therapeutic strategies to target de-differentiated cells and prevent BLBC from occurring. 

Dr. Guo is professor of cell biology and a member of the Ruth L. and David S. Gottesman Institute for Stem Cell Research and Regenerative Medicine at Einstein, and a member of the Cancer Dormancy Institute and the Marilyn and Stanley M. Katz Institute for Immunotherapy for Cancer and Inflammatory Disorders at the National Cancer Institute–designated Montefiore Einstein Comprehensive Cancer Center. (1R01CA289734-01A1)