# The origins of metabolic reprogramming in prostate cancer

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $449,272

## Abstract

PROJECT SUMMARY
Approximately 29,000 men in the United States were estimated to die from prostate cancer in 2018. As our
current therapies are not working for a large number of men with metastatic castration-resistant prostate cancer,
we need innovative strategies to identify new therapeutic approaches. Advances in dissecting mechanisms of
metabolic reprogramming in several tumor types has led to widespread interest in drugging metabolic
vulnerabilities as a therapeutic strategy for cancer. Defining the factors that regulate metabolic reprogramming
in prostate cancer is fundamental to understanding prostate cancer pathogenesis and likely to yield therapeutic
targets for this lethal disease. Two key factors that regulate metabolic reprogramming in cancer and inform
metabolic vulnerabilities that can be targeted for therapy are the disease-initiating oncogenes and the tissue or
cells-of-origin. However, it is not well understood how the cells-of-origin for prostate cancer cooperate with
oncogenes to reprogram metabolism. Using genetically engineered mouse models and human transformation
assays, we and others have demonstrated that both prostate basal and luminal cells can serve as target cells
for prostate transformation. Genetically altered basal cells must differentiate into luminal cells in order to initiate
cancer, establishing a key role for differentiation in basal cell-initiated tumorigenesis. In response to hormonal
therapy, luminal-like prostate cancer cells undergo lineage plasticity and exhibit basal cell features,
demonstrating a role for differentiation in disease progression and therapy-resistance. Surprisingly, little is known
about (1) metabolic activity in distinct epithelial cells of the prostate, (2) how changes in metabolism regulate
epithelial differentiation, and (3) how oncogenic transformation reprograms prostate epithelial metabolism.
Understanding prostate cancer metabolism requires first understanding prostate epithelial metabolism. However,
such data on the metabolism of primary cell-types does not yet exist. In this proposal, mouse and human tissue
will be studied in parallel to determine the extent to which the cells-of-origin and the disease-initiating oncogenes
regulate metabolic reprogramming in prostate cancer. In Aim 1, we will establish metabolic signatures of distinct
cells-of-origin for prostate cancer (basal and luminal). In Aim 2, we will evaluate metabolic regulation of luminal
differentiation, a requirement for prostate tumorigenesis. In Aim 3, we will determine how epithelial metabolism
is reprogrammed in response to genetic alterations. This novel approach will enhance our fundamental
understanding of prostate tumorigenesis and may lead to new therapeutic strategies to combat lethal prostate
cancer.

## Key facts

- **NIH application ID:** 10213672
- **Project number:** 5R01CA237191-03
- **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:** $449,272
- **Award type:** 5
- **Project period:** 2019-08-02 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10213672

## Citation

> US National Institutes of Health, RePORTER application 10213672, The origins of metabolic reprogramming in prostate cancer (5R01CA237191-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10213672. Licensed CC0.

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