# Identification of serum protein biomarkers by profiling N-glycoproteomes of patient-derived xenografts of neuroendocrine prostate cancer > **NIH NIH R21** · STANFORD UNIVERSITY · 2024 · $171,759 ## Abstract PROJECT SUMMARY Neuroendocrine prostate cancer (NEPC) is a lethal variant of prostate cancer (PCa) that may arise de novo or in 17-30% of patients previously treated with standard of care androgen deprivation therapy (ADT) for prostate adenocarcinoma (AC) as a mechanism of resistance. Serum biomarkers with high sensitivity and specificity for non-invasive detection for NEPC are urgently needed to enable clinicians to select the proper next-line systemic therapy in a timely manner, select of patients for clinical trials, and monitor treatment responses that entail reversing the NEPC state. A novel strategy that allows quick identification of ‘‘human- unique’’ proteins in a mouse serum background, thereby overcoming limitations associated with proteomics- based biomarker discovery, has been used successfully to identify serum glycoprotein biomarkers in ovarian cancer patient-derived xenografts (PDX). We hypothesize that PCa PDX tumors that reflect human PCa express unique tumor-associated glycoproteins that can be readily identified in sera of tumor-bearing mice using mass spectrometry. Moreover, different serum glycoproteins and their levels are associated with different subtypes of PCa PDXs, namely, pure AC, AC mixed with NEPC, and pure NEPC. Finally, these subtype specific biomarkers can be used to identify NEPC in clinical samples from PCa patients. In Aim 1, we will identify novel serum glycoproteins associated with subtypes of PCa PDX tumors by glycoproteomic analyses of PDX sera. Specifically, PDX tumors will be generated using cryopreserved tissues from publically available PDXs lines with pure AC, AC mixed with NEPC and pure NEPC histology by subrenal implantation into immunodeficient mice. Quantitative proteomics will be performed to generate glycoproteomic profiles of PDX sera and human-specific proteins will be selected bioinformatically. In Aim 2, serum proteins found in samples with a NEPC component but not expressed in pure AC samples will be selected. The top 5 candidate NEPC-specific biomarkers for which a targeted assay is developed successfully will be validated in sera from PDX mice and patients with pathologically confirmed NEPC component. The sensitivity and specificity of these biomarkers will be assessed using sera from patients with pathologically confirmed AC and benign prostatic hyperplasia as true negative control. Our approach would lead to biomarkers that could be developed quickly for use in the clinic to reduce morbid biopsies and appropriately triage patients to therapies tailored to their disease state, which in turn, will improve quality of life and survival. In addition, these biomarkers could be used to monitor patient response to standard-of-care therapies and select patients for clinical trials testing novel therapies developed in the future that target NEPC specifically. Moreover, the subtype-specific glycoproteins we identified could serve as the basis for future imaging strategies or targeted therapies. ... ## Key facts - **NIH application ID:** 10783009 - **Project number:** 5R21CA276896-02 - **Recipient organization:** STANFORD UNIVERSITY - **Principal Investigator:** JAMES D. BROOKS - **Activity code:** R21 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $171,759 - **Award type:** 5 - **Project period:** 2023-02-15 → 2025-01-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10783009 ## Citation > US National Institutes of Health, RePORTER application 10783009, Identification of serum protein biomarkers by profiling N-glycoproteomes of patient-derived xenografts of neuroendocrine prostate cancer (5R21CA276896-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10783009. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*