We focus on how stromal cells drive tumor progression and modify the host immune response to tumor cells
Immune cells are found adjacent to senescent cells in human skin (left). A pattern that is similar to what we find in the FASST mouse (right). Further analyses suggest that these cells are immunosuppressive raising the possibility that they contribute to cancer.
While estrogen is important for bone homeostasis, woman treated with chemotherapy lose significantly more bone than woman in menopause. We show that chemotherapy-induced senescence drives bone loss. We can rescue chemotherapy-induced bone loss by killing senescent cells or inhibiting the p38MAPK/MK2 pathways.
p38MAPK and MK2 inhibitors limit breast cancer metastasis and preserve bone integrity. When we combine p38i and angonist anti-OX40 we significantly limit metastatic growth in bone and visceral organs.
Following treatment of primary breast cancer, up to 20% of patients can experience a recurrence 6 months to 25 years later. What maintains tumor cell dormancy and what drives indolent disease to reactivate? It is clear that both cell autonomous and extrinsic factors impact breast cancer tumor cell dormancy. We are studying both aspects of tumor cell dormancy.