Co-Leaders Dr. Himisha Beltran, Dr. Francesca Demichelis, and Dr. Scott Tagawa 

Identifying patients with advanced prostate cancer who will no longer benefit from potent androgen receptor (AR)-directed therapies is a clinical unmet need. This study will systematically assess the biologic and clinical impact of dynamic neuroendocrine prostate cancer genomic signature changes using plasma DNA specimens from a prospective cohort of patients. This will lead to the clinical development of a plasma biomarker with several areas of potential impact including earlier detection of patients progressing towards treatment resistance which would identify advanced prostate cancer patients unlikely to benefit from additional AR-targeted strategies and would select high-risk patients for targeted treatment for neuroendocrine-directed or co-targeting approaches.

Project 1 will lead to the development of a non-invasive genomic biomarker with several areas of potential impact, including early detection of patients transforming toward AR-independence and leading to early cessation of AR therapy and/or consideration of metastatic biopsy to look for neuroendocrine transformation and selection of treatment with platinum-based therapies or other targeted approaches.

Specific Aims: 

AIM 1: Determine tumor dynamics and the clinical impact of circulating alterations in predicting response to AR-directed therapy;

AIM 2: Define the spectrum of circulating DNA alterations in patients with advanced prostate cancer.