Translating Immunotherapy to Breast Cancer: Mechanisms, Biomarkers, and Rationally Designed Therapeutic Combinations
Abstract
The field of breast cancer research has made remarkable discoveries and advances in the last 20 years that span basic, clinical, and epidemiologic sciences. New biomarkers, treatments, and clinical options have been developed, and many patients can now be cured of breast cancer through advances in early detection, drug and radiation therapy, and surgical resection. However, despite higher cure rates and more effective therapies, there are a number of barriers that persist in the treatment of breast cancer. Although these obstacles span all stages of breast cancer, the most critical and challenging of these is how to best treat metastatic disease. It is important to remember that it is nearly always metastatic disease, not the primary tumor, which claims the lives of breast cancer patients. Thus, the future of breast cancer research must include strategies for better treating metastatic disease. Although we now have a better understanding of how and why breast cancer metastasizes, we know that metastasis nearly always occurs before the patient is diagnosed. Even in patients who have had successful surgical removal of the primary tumor, breast cancer still recurs in the form of distant metastases months or years later. No matter how many advances are made along the spectrum of breast cancer research (e.g., from early detection and screening, to early-line curative therapies), some fraction of patients will ultimately present with metastatic disease. Thus, the most mission-critical aspect of breast cancer research is to identify therapies that can eliminate breast cancer metastases and produced long-lived “durable” responses. Taking evidence from other highly aggressive tumor types with high death rates, we believe “immunotherapy” is the optimal approach to treat metastatic disease in breast cancer patients, and in the right combination, could cure late-stage patients. My research program tests this hypothesis, from cell line and mouse models, all the way to clinical trials in patients. Immunotherapy is a broad terminology that covers many aspects of immunologically active therapies, including vaccines, biologics, cytokine therapy, and cellular therapy. So far, one of the most promising immunotherapies to date are antibodies targeting proteins called PD-1 and PD-L1. Patients experiencing clinical responses to these agents can sometimes have complete eradication of cancer lasting for years, and many other patients experience permanent slowed growth of their tumor(s). In early phase clinical trials of metastatic breast cancer, similar responses were observed, albeit only in a small population of patients. This signal suggests that immunotherapy-driven combinations could be the next breakthrough in the treatment of metastatic breast cancer. Identifying why and how some breast cancers respond to immunotherapy and how to make more patients respond using “smart” combinations is the focus of my laboratory, and this proposal.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810149
Entities
People
- Justin Balko
Organizations
- United States Army
- Vanderbilt University