# A Prostate Cancer Dependency Map to Identify Tumor Subtype-Specific Vulnerabilities

> **NIH NIH R21** · FRED HUTCHINSON CANCER CENTER · 2024 · $195,415

## Abstract

PROJECT SUMMARY/ABSTRACT
Despite the advances in our knowledge of cancer biology and the approval of new cancer drugs by the Food
and Drug Administration (FDA), very few patients with solid tumors that have spread to distant sites
(metastases) are cured of their disease. This is true of metastatic prostate cancer (mPC). Consequently,
substantial research is directed toward identifying new targets and treatments.
 New technologies which we and others have developed, now provide unprecedented approaches for
deeply characterizing tumors on a comprehensive scale. Studies using these approaches have determined
that mPC is comprised of multiple distinct subtypes – a subset of these are defined by specific genomic
alterations in oncogenes and genes that normally function to suppress tumor growth. Others are defined by the
phenotype – characteristics that influence function and behavior. Notably, a number of these subtypes are now
known to have different vulnerabilities to particular therapies – knowledge that underlies a more precision
approach for treatment. However, for most subtypes we do not currently have knowledge of their particular
vulnerabilities nor do we have therapeutics that can halt their growth/progression.
 Powerful high-throughput approaches to dissect the function of every gene in a particular cancer genome
have been deployed to construct cancer dependency maps (DEPMAP) in many cancer types. These
approaches are highly ‘discovery driven’ as they approach the problem of identifying cancer vulnerabilities in a
systematic rather than hypothesis-driven fashion. However, prostate cancer is largely excluded from these
International projects due to the very limited number of mPC models available to conduct these large scale
experiments.
 In this proposal, we aim to identify new treatment avenues for advanced lethal prostate cancer. We will use
multiple new models of metastatic prostate cancer that we have developed and characterized to identify PC
subtype specific dependencies using genome-wide loss-of-function screens. In parallel, we will evaluate
growth inhibitory effects of drug libraries of approved agents as well as compounds in development.
Combinations of agents that exploit genomic dependencies will be tested in vivo against a panel of patient
derived xenograft (PDX) lines with and without the predicted vulnerability.

## Key facts

- **NIH application ID:** 10770374
- **Project number:** 5R21CA277368-02
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** PETER S NELSON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $195,415
- **Award type:** 5
- **Project period:** 2023-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10770374

## Citation

> US National Institutes of Health, RePORTER application 10770374, A Prostate Cancer Dependency Map to Identify Tumor Subtype-Specific Vulnerabilities (5R21CA277368-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10770374. Licensed CC0.

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