Exploiting the Immune Microenvironment Variation in Subtypes of Metastatic Prostate Cancer
Abstract
Scientific Objective and Rationale: This research project is designed to further scientific knowledge concerning the immune system in advanced prostate cancer (PC) and to develop approaches that can harness the immune system to eradicate what is currently incurable cancer. PC that has spread to distant sites in the body (e.g., bone) is termed metastatic cancer. Men with metastatic PC respond initially to conventional treatment such as chemotherapy, but always progress to incurable lethal disease. Of importance, we now recognize that metastatic PC can be divided into many different subtypes. Certain subtypes respond to specific types of therapies, whereas other subtypes resist these treatments – a fact that underlies the concept of precision or personalized medicine. One subtype of metastatic PC responds to a type of immune therapy termed immune checkpoint blockade (ICB). ICB has revolutionized cancer treatment and, in several cancer types such as melanoma, ICB has resulted in cures. Unfortunately, the PC subtype that responds to ICB is rare. In preliminary work conducted to support this application, we found that different subtypes of metastatic PCs have distinct immune cell landscapes that include immune targets that have yet to be evaluated in PC. The research objectives are to (1) fully characterize the immune landscapes of metastatic PC subtypes; (2) determine whether PC subtypes dictate the composition of their immune environments; and (3) determine whether targeting PC type-specific immune features will inhibit tumor growth. I will specifically test two approaches using FDA-approved drugs or those currently in clinical trials such so that the findings can be rapidly repositioned to support clinical studies in men with advanced PC. Results from this project will contribute vital information towards personalized therapeutic strategies for patients with advanced and currently incurable PC. Applicability of Research: This research is applicable to patients diagnosed with PC that have progressed to the stage that they are no longer responding to conventional therapies. Further, it is applicable to patients for whom their PC has developed into different subtypes termed neuroendocrine or double-negative PC. The goal of this research is to further our understanding of the immune cell profiles of PC by testing for the presence of distinct immune cell types and specific patterns present in the tissue samples taken from metastatic biopsy sites. Results of these studies will contribute vital information towards personalized therapeutic strategies for patients. Successful accomplishment of these aims will provide patient-specific information to help direct treatment by utilizing existing approved therapies and consequently improve overall survival and quality-of-life. Principal Investigator’s Goals in Prostate Cancer Research: My overall career goal is to become an independent PC researcher leading a multi-disciplinary team with a focus on bringing advances in the laboratory directly to patients (“bench to bedside”). My aim is to improve not only quantifiable aspects of disease progression (e.g., overall survival, therapy response), but to minimize the qualitative side effects (e.g., stress, fatigue) of treatment that impact quality of life. The field of immuno-oncology has shown the potential to dramatically improve the outcomes of several types of cancer, thereby demonstrating potential. I aim to determine how immune-based therapeutics can be leveraged to impact advanced prostate cancer. I aspire to remain at the interface of translational clinical medicine and patient-focused care and hope to push the boundaries of technological advancements to both inform treatment strategy and improve day-to-day life of those with this disease. One such advancement is digital spatial profiling, on which I have gained proficiency in identifying cellular profiles that will provide relevant insight when investigating th
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110028
Entities
People
- Lauren Brady
Organizations
- Fred Hutchinson Cancer Center
- United States Army