The mammary cell secretome as a novel biologic for triple-negative breast cancer

SUMMARY Breast cancer accounts for nearly a quarter of all cancers in women and it remains the second leading cause of cancer deaths in the US, despite substantial changes in standard of care treatments. Identifying evolutionary mechanisms that naturally protect species from developing cancer is becoming an increasingly appreciated

approach to develop therapeutic strategies that are both efficient and non-toxic. We recently identified a cancer- suppressing mechanism based on the secretion of bioactive factors with anti-cancer activity by mammary cells (aka. mammosphere-derived epithelial cells or MDECs) from domesticated mammary cancer-proof mammals.

Specifically, these bioactive factors were shown to (i) induce triple negative breast cancer (TNBC) cell death, without affecting normal human breast cells, in vitro and (ii) reduce tumorigenicity in a xenograft TNBC mouse model in vivo. These findings led to our central hypothesis that the MDEC secretome from mammary cancer-

proof mammals has significant potential for the development of novel effective and non-toxic therapies to treat and/or prevent breast cancer, especially the aggressive and hormone therapy-unresponsive TNBC. We now propose to follow up on these interesting findings by further characterizing the anti-cancer activity of the MDEC

secretome in greater depth (Aim 1) and evaluating the therapeutic and/or preventative effects of the MDEC secretome in mouse models of TNBC (Aim 2). The significance of this application lies in the novelty of the approach being used to identify non-toxic efficient breast cancer therapeutic and/or preventative interventions

by focusing on bioactive anti-cancer factors produced by normal mammary cells from mammary cancer-proof mammals. The proposed experiments will increase our knowledge of novel cancer-suppressing mechanisms and will provide a solid basis for the design of effective and non-toxic therapies that can be used to fight

aggressive TNBC and/or for the development of protective factor-based therapeutics to eliminate or reduce TNBC in high-risk populations.