Molecular and Clinical Correlates with Prostate-Specific Membrane Antigen (PSMA)-Targeted Radionuclide Therapy
Abstract
Prostate-specific membrane antigen (PSMA) targeted radionuclide therapy (TRT) builds upon the radiosensitivity of prostate cancer with the specific expression of PSMA. We hypothesize that there are patient (germline) and/or tumor molecular characteristics such as DNA repair defects and active AR signaling as well as clinical characteristics that are associated with response (or lack thereof) to PSMA-TRT. We hypothesize that quantitative molecular imaging assessment of PSMA expression will be associated with response to PSMA-TRT. We also hypothesize that PSMA-TRT generates an immune response that may be identified and associated with patient outcome. In this proposal, we will utilize our retrospective and prospective data and sample sets to: assess genomic biomarkers and gene expression changes associated with outcome from anti-PSMA targeted radionuclide therapy; assess clinical parameters associated with outcome from anti-PSMA- TRT; assess PSMA expression as determined by PSMA molecular imaging associated with response to anti-PSMA TRT; and (iv) evaluate generation of an immune response following anti-PSMA-TRT in association with clinical outcome. This project addresses the overarching challenge to develop effective new treatments and address mechanisms of resistance and particularly addresses the Focus Areas of Imaging and Targeted Radionuclide Therapy and Therapy and Mechanisms of Resistance and Response. As it is clear that prostate cancer is a radiosensitive disease, and PSMA is highly and selectively expressed, but not all patients respond to PSMA TRT, this proposal will rapidly translate into clinical progress for men afflicted with advanced prostate cancer in the near term. Furthermore, such targeted therapy may lead to future cures for men with micrometastatic disease in the high-risk clinically localized or biochemically recurrent settings.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1228216
Entities
People
- Himisha Beltran
- Neil H Bander
- Scott T Tagawa
Organizations
- Cornell University