Detection of the Glucocorticoid Receptor with PET in Treatment-Resistant Castration-Resistant Prostate Cancer
Abstract
The purpose of this project is to implement a new imaging strategy using positron emission tomography to identify the subset of metastatic castration-resistant prostate cancer that develops resistance to standard of care therapies by activating a protein called the glucocorticoid receptor. The urgency to develop this technology was motivated by three considerations. First, current diagnostic technologies only report on whether the patient’s tumor ceases to respond to therapy, and they do not reveal the biological reason why the tumor has stopped responding. This is a crucial gap in patient care, as there are many known biological reasons why a prostate cancer tumor may fail to respond, and these different mechanisms each require specialized follow-up treatment approaches. Therefore, this technology is responsive to the unmet need to identify biologically why a patient’s tumor is resistant so an appropriate follow-up therapeutic course can be sensibly implemented. Second, three new inhibitors of the glucocorticoid receptor are currently being tested in patients with castration-resistant prostate cancer. Therefore, this imaging technology is very timely and impactful, as it can be immediately positioned alongside or within these clinical trials to identify patients whose tumors would be most likely to respond to these exciting new therapies. Last, the imaging technology can also be applied easily and safely several times to the same patient. Thus, the technology can be applied after the start of therapy to determine whether the dose is completely suppressing the target or whether further adjusting of the dose is required to ensure the best possible tumor responses. While this project does not constitute a clinical trial, a major goal for the project period is to collect human imaging data in patients with treatment-resistant metastatic castration-resistant prostate cancer. With these feasibility data, it is reasonable to expect that this technology could impact patient-related outcomes within 3 years after the end of the project. Moreover, as standard-of-care therapies like enzalutamide and apalutamide are administered to patients with metastatic castration-sensitive prostate cancer, the imaging technology will likely become useful to test in this patient population for evidence of glucocorticoid receptor-driven resistance. In summary, this is a translational research project that will, for the first time, enable a precise, patient by patient, characterization of a prominent resistance mechanism using an imaging modality that is highly accessible to cancer patients of all socioeconomic backgrounds. In this respect, the project is directly responsive to the Overarching Challenges of “define the biology of lethal prostate cancer to reduce death” and “develop treatments that improve outcomes for men with lethal prostate cancer.”
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010354
Entities
People
- Michael J. Evans
Organizations
- United States Army
- University of California, San Francisco