The Epigenetic Adaptation of ER+ Breast Cancer Cells to the Bone Microenvironment
Abstract
Bone metastases more frequently occur to estrogen receptor positive (ER+) breast cancer. Thus, it is imperative to understand how disseminated ER+ cancer cells escape therapies in distant organs and to identify therapies that can eliminate these cells. Supported by the DoD Era of Hope Award, my laboratory developed a series of models and techniques to investigate cancer-bone interaction at a single cell resolution. We have also elucidated an epigenomic reprogramming effect elicited by the bone microenvironment that leads to endocrine resistance. Importantly, this represents a mechanism fundamentally distinct from classic clonal evolution process. In this application, we aim to expand our research to understand the epigenetic mechanisms underlying the above mentioned effects. More importantly, we wish to identify therapeutic strategies that can reverse the endocrine resistance and prevent recurrences of ER+ breast cancer. It is important to note that multiple lines of evidence have emerged and suggest that many metastases are actually seeded by other metastases, rather than primary tumors. Two thirds of bone-only metastases are followed by appearance of metastases in multiple other organs. Our unpublished studies also demonstrated that bone microenvironment may invigorate disseminated breast cancer cells for further metastasis. Thus, our research focusing on bone metastasis may indeed generate broader impact and lead to reduction of metastases in other organs as well. Taken together, the proposed research represents a move beyond incremental advancement, and will likely lead to new metastatic and adjuvant therapies. Our study will demonstrate how epigenomic adaptation drives cancer evolution and alter therapeutic responses together with clonal selection, provides insights into the clinical enigma of ER+ metastatic recurrences despite endocrine therapies, and leads to reduction of metastasis-related breast cancer mortality.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2021
- Accession Number
- AD1147536
Entities
People
- Xiang Zhang
Organizations
- Baylor College of Medicine