Abstract 6563: PSMA-based detection and global proteome-based analysis of circulating tumor cells in castration resistant prostate cancer patients

Abstract In recent years, many new targeted and immuno-therapies have entered the cancer treatment landscape with the potential to drastically improve patient outcomes; however, selecting the optimal drug target especially as the disease progresses becomes increasingly important. Liquid biopsies show great promise in providing insights on the current disease state, but generally rely on a small number of protein markers identified through immunofluorescence staining or genomic mutations determined from cell-free DNA which limits the amount of information available to make treatment decisions. One way to better select the optimal drug target is to generate unbiased mass-spectrometry based proteomic data from the circulating tumor cells (CTCs) isolated from blood. In this study, we collaborated with Astrin Biosciences using their patented isolation technology to enrich CTCs with high purity from the blood of 57 metastatic castration resistant prostate cancer (mCRPC) patients. The CTC-enriched sample (along with a patient-matched control sample consisting primarily of white blood cells) was analyzed in real time for either PSMA protein (Lutetium-PSMA-617 study, n=32) or via mass-spectrometry (CTC proteomics study, n=25). Over 1,500 peptides corresponding to greater than 600 proteins were identified from each patient’s CTCs. These included increased epithelial cell markers in the CTC-enriched sample and increased WBC markers in the control sample. Specifically, detection of the androgen receptor protein was identified in the CTC-enriched sample which is of particular interest in mCRPC patients. Furthermore, this method is able to detect and quantify PSMA expression, which is of clear relevance in the context of PSMA-directed therapeutics. This study demonstrates the feasibility of obtaining large scale proteomic data from a liquid biopsy. Future studies will focus on cancer signaling mechanisms and biomarkers to elucidate the clinical utility of such data. As more patients are analyzed, we will compare proteomic data with known tissue proteome information when available and to correlate these with drug response to improve treatment selection and patient outcomes. Citation Format: Justin M. Drake, Ali Arafa, Alec Horrmann, Kaylee J. Kamalanathan, Catalina Galeano-Garces, Zoi Sychev, Nicholas Heller, Mahdi Ahmadi, Megan Ludwig, Olivia Hedeen, Alexa Hesch, Grant Schaap, Joel Hapke, Jeff Miller, Ivo Babris, Tuan Lee, Tony Clacko, Justin Hwang, Jiarong Hong, Badri Konety, Jayant Parthasarathy, Emmanuel Antonarakis. PSMA-based detection and global proteome-based analysis of circulating tumor cells in castration resistant prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6563.