# Project 3: Towards Understanding Prostate Cancer Heterogeneity

> **NIH NIH P50** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $346,460

## Abstract

PROJECT 3: SUMMARY
Although high risk localized prostate cancer (PCa) is often cured by multimodal therapy including radical
prostatectomy, radiation therapy [RT] and androgen deprivation therapy [ADT], the development of castration
resistant prostate cancer (CRPC) after metastatic progression is lethal. Studies from several groups have
profiled untreated localized PCa and CRPC, however these studies represent static snapshots from convenient
samples or rapid autopsies from earlier treatment eras. Lacking are molecular studies addressing PCa
progression during current treatments or clinical trials. Recently, a multi-institutional “Dream Team” was formed
to perform whole exome (WES) and RNA sequencing on metastatic tumor biopsies (and germline DNA) from
500 CRPC patients (the “CRPC500” study) prior to enrollment on trials involving enzalutamide, abiraterone,
and a PARP inhibitor (olaparib). We recently published the first 150 cases (Robinson et al., Cell 2015) and
over 500 men have been enrolled with clinical follow-up expected through the next 3 years. We now have the
extraordinary opportunity to examine the original untreated diagnostic material from the prostates of the
CRPC500 patients and compare it to the metastatic samples to explore key critical questions relevant to
progression to CRPC and treatment response.
Our team developed next generation sequencing (NGS) assays enabling interrogation of formalin-fixed paraffin
embedded (FFPE) samples. EXaCT-1 is a CLEP (CLIA) approved WES assay with an associated analysis
pipeline used on over 700 metastatic and primary sample/normal pairs (Weill Cornell Medicine).
Complementing this assay is a PCa-specific version of the Oncomine Cancer Panel optimized for 10-20ng
FFPE DNA and RNA (Univ. Michigan). These approaches allow analysis of untreated primary tumors from
CRPC500 patients. Our overarching goal is to determine the extent to which early mutations/other molecular
alterations inform on disease progression and response to AR or PARP directed therapy.!

## Key facts

- **NIH application ID:** 10227731
- **Project number:** 5P50CA211024-05
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** MARK A. RUBIN
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $346,460
- **Award type:** 5
- **Project period:** 2017-08-30 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10227731

## Citation

> US National Institutes of Health, RePORTER application 10227731, Project 3: Towards Understanding Prostate Cancer Heterogeneity (5P50CA211024-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10227731. Licensed CC0.

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