# Patient-Derived Models of Prostate Cancer for Personalized Medicine

> **NIH NIH U01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $1,026,019

## Abstract

PROJECT SUMMARY/ABSTRACT
Metastatic prostate cancer (PCa) that progresses after androgen ablation therapy (i.e., castration-resistant
PCa [CRPC]) remains incurable. Gaining a mechanistic understanding of PCa progression has been
hampered by a lack of clinically relevant PCa models. Recently, patient-derived models of cancer (PDMCs;
e.g., patient-derived xenografts [PDXs] and organoids) have been used to develop therapeutically relevant
approaches. We hypothesize that longitudinal studies of tumor specimens (and corresponding PDMCs)
obtained over time from the same patient will lead to a better understanding of the diverse dominant pathways
that drive metastatic progression. We also hypothesize that organoids will complement PDXs as part of an
integrated analysis of human tissue and derived PDMCs (obtained at single time points) to understand the
mechanisms of response and resistance to target pathways commonly activated in CRPC. We will test these
hypotheses through the following specific aims: Aim 1. Analyze human donor tumors and corresponding
PDMCs to identify dominant molecular alterations that drive PCa progression and select models to study. We
will develop PDMCs from clinically annotated tumor specimens derived from men with potentially lethal PCa,
including PDMCs derived from tumor specimens obtained at different times during progression (longitudinal
studies) and from different areas of the same tumor. We will assess human PCa specimens and PDMCs’
morphology and expression of genes associated with PCa progression and subject them to whole-exome
sequencing and RNA sequencing. PCa specimens and PDMCs derived from the longitudinal studies will also
be subjected to whole-genome sequencing and epigenomic analysis. Finally, we will develop a publicly
available interactive database linking molecular and preclinical results of PDMC characterization with clinical
and molecular details of donor human PCa. These studies' findings will serve as the basis for the identification
and prioritization of aberrant molecular pathways for further study. This knowledge is also essential to
understanding how each PDMC provides information about the alterations in human donor tumor. Aim 2.
Study genomic alterations acquired in metastasis specimens in the longitudinal studies for their potential to
confer metastatic ability to cells. We will genetically modify organoids to create the genomic alterations found in
the metastases. We will subsequently study how the genetic modification of these genes influences specific
steps involved in metastasis, namely invasion, migration, and ability to grow at distant sites. Aim 3. Utilize
PDMCs to study mechanisms of PCa response/resistance to targeted therapies on pathways implicated in PCa
progression. We will seek a mechanistic understanding of PCa response and/or resistance to therapies in
clinical trials targeting the AR, DNA damage response, Wnt-canonical, and PI3K pathways. These studies will
inform the discovery and ...

## Key facts

- **NIH application ID:** 10219178
- **Project number:** 5U01CA224044-03
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Yu Chen
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,026,019
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219178

## Citation

> US National Institutes of Health, RePORTER application 10219178, Patient-Derived Models of Prostate Cancer for Personalized Medicine (5U01CA224044-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10219178. Licensed CC0.

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