Novel Therapies Targeting the Stromal Compartment of Metastatic Breast Cancer
Abstract
Cancer results from mutations in the DNA of developing cancer cells and changes in the normal cells that surround them. Using unique inhibitors of the p38MAPK pathway (a pathway in a cell that is activated when cells are presented with a wide array of stress), we recently showed that we could target normal cells that have been coopted to support metastatic breast cancer growth in preclinical animal models. We found that when we targeted these normal cells with these inhibitors, we significantly limited metastatic tumor growth and extended survival. Because we know from previous work that these normal cells can limit the ability of the immune system to attack tumor cells, we now ask if these normal cells contribute to the failure of immunotherapy in the breast cancer setting. Thus, we propose to ask if we can combine our p38MAPK inhibitors with immunotherapy and unleash the incredible killing power of the human immune system to further reduce metastatic breast cancer growth. Because the inhibitors under investigation are well tolerated in patients with nonlethal diseases such as COPD, we will take these findings and design a first-in-human clinical trial in the metastatic breast cancer setting. For patients suffering from other forms of cancer, immunotherapy is turning the tide and offering the possibility of a cure or sustained disease free survival. Unfortunately these same advances have not proven successful in breast cancer. If we are to increase survival rates of breast cancer patients, we need to figure out how to awaken the extraordinary killing power of the patient’s own immune system and annihilate the tumor cells wherever they metastasize throughout the body. This proposal will uncover the mechanisms by which normal cells limit the immune response in breast cancer and lead to novel approaches to bring effective immunotherapies to breast cancer patients.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910688
Entities
People
- Sheila Stewart
Organizations
- United States Army
- Washington University in St. Louis