The Role of Mesenchymal Stem Cells in Radioresistance of Breast Cancer Bone Metastasis
Abstract
Breast cancer is the second most common newly diagnosed cancer and second leading cause of cancer death among women in the United States. This malignancy is a major health threat worldwide because of its high incidence rate and the constant risk of recurrence. Bone metastasis frequently occurs in breast cancer patients, and radiotherapy is one of the primary treatment choices for them. Unfortunately, breast cancer patients with bone metastases often suffer from local recurrence or metastatic relapse in other bone locations or distant organs after treatments. Tumor cells are localized within a specialized environment, which includes immune cells and multiple types of supporting cells. Among the supporting cells, mesenchymal stromal cells (MSCs) recently emerged as a key component of tumor environment due to their bidirectional interaction with the tumor-associated immune cells in promotion of primary tumor growth. In addition, scientists recently realized that the resistance of many breast cancer patients against various therapies is mainly caused by tumor environment. Therefore, how to therapeutically target MSC becomes a key question for current breast cancer therapy. While tumor-bone crosstalk has been studied extensively in the context of primary tumor growth and bone metastasis formation, very few studies have explored such interactions in the context of common cancer therapeutics such as radiotherapy, one of the principle treatment options for patients with bone metastases. The proposed study will build on our extensive experience in the study of tumor-stromal interactions in breast cancer bone metastasis and will investigate the poorly explored questions of how radiotherapy-induced bone marrow mesenchymal stem cells (BM-MSCs) changes influence the resistance and early relapse of tumor cells in bone. Our proposed studies will provide novel insights into the poorly understood question of how a traditional cancer treatment approach, radiotherapy, alters the bone marrow microenvironment, particularly BM-MSCs, and subsequently affect recurrence and relapse of bone metastasis. The results from the proposed research will therefore address the following overarching challenges: (1) identify why some breast cancers become metastasis; (2) revolutionize treatment regimens by replacing interventions that have toxicities with ones that are safe and effective; (3) eliminate the mortality associated with metastatic breast cancer. My long-term goal is to become an independent breast cancer researcher leading my own research team to help eliminate the deadly metastasis of breast cancer. I recently completed my Ph.D. and postdoctoral trainings in the field of female reproduction at Baylor College of Medicine. I have successfully established several new mouse models with conditional deletion of the TGFß superfamily receptors in the female reproductive system. One of the mouse models developed endometrial cancer, and the primary cancer metastasized to the lungs. These findings led me to the intriguing field of cancer biology, especially from cancers associated with women. I developed a strong interest in the study of breast cancer, which is the most common invasive cancer in females worldwide. Therefore, I chose Dr. Yibin Kang s laboratory at Princeton University for my next postdoctoral training to develop my research expertise in understanding the molecular mechanisms of breast cancer progression and metastasis. Dr. Kang is a leading scientist in the field of breast cancer metastasis research. His outstanding achievements in innovative research on breast cancer metastasis have been recognized by many prestigious awards, including the 2006 Breast Cancer Research Program Era of Hope Scholar Award, the 2011 Vilcek Prize for Creative Promise in Biomedical Sciences, the 2012 American Association for Cancer Research (AACR) Award for Outstanding Achievement in Cancer Research, the 2014 Fidler Innovation Award by the Metast
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810009
Entities
People
- Peng Jia
Organizations
- Princeton University
- United States Army