# The Origins of Metabolic Reprogramming in Prostate Cancer

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $76,736

## Abstract

PROJECT SUMMARY
More than 33,000 individuals in the United States were estimated to die from prostate cancer in 2020,
predominantly due to treatment-resistance. As our current therapies are not working for a large number of
patients with metastatic castration-resistant prostate cancer, we need innovative strategies to identify new
therapeutic approaches. Suppression of the androgen signaling axis with potent androgen receptor pathway
inhibitors (ARPIs) has increasingly led to the outgrowth of AR-indifferent tumors that exhibit loss of luminal
features and gain of basal and/or neuroendocrine features, termed lineage plasticity or lineage infidelity. Limited
knowledge of the factors regulating lineage identity in prostate epithelium has stalled efforts to prevent or reverse
lineage plasticity, promote sensitivity to ARPIs, and reduce lethality in CRPC. This proposal stems from our
discovery that altering fuel preference is sufficient to modulate lineage identity in prostate epithelium, based on
early results from the parent R01. We hypothesize that fuel preference regulates lineage identity and may
modulate resistance to ARPIs in CRPC. In Aim 1, we will utilize a 3D organoid assay to modulate fuel preference
and define transcriptional and proteomic changes to evaluate lineage identity in normal prostate epithelium. In
Aim 2, we will utilize distinct genetic models of prostate cancer driven by tumor suppressor loss (Pten, Rb1) to
determine how fuel preference modulates prostate cancer lineage identity. Defining the factors that regulate
lineage identity is fundamental to understanding prostate cancer treatment-resistance and may yield therapeutic
targets for this lethal disease.

## Key facts

- **NIH application ID:** 10310816
- **Project number:** 3R01CA237191-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Andrew S Goldstein
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $76,736
- **Award type:** 3
- **Project period:** 2019-08-02 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10310816

## Citation

> US National Institutes of Health, RePORTER application 10310816, The Origins of Metabolic Reprogramming in Prostate Cancer (3R01CA237191-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10310816. Licensed CC0.

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