# Therapeutic targeting of tumor metabolism in advanced prostate cancer

> **NIH VA I01** · VA NORTHERN CALIFORNIA HEALTH CARE SYS · 2021 · —

## Abstract

Advanced prostate cancers disproportionally affect veteran populations in the US. One key feature of the
advanced diseases is an aberrantly elevated cholesterol biosynthesis for the tumor, which likely contributes
to the lethal progression of prostate cancer. However, the mechanisms underlying the aberration are poorly
understood, which severely hinders exploitation of the unique metabolic vulnerability for effectively
therapeutic intervention of advanced diseases. Epidemiological evidence from retrospective studies,
including ones in the veterans populations, generally associate cholesterol-lowering drug statin use with
improved survival and/or lower risk of advanced disease. However, thus far, clinical trials targeting
advanced tumor cholesterol synthesis with statins have not yet yielded significant benefits to patients.
Therefore, identification and elucidation of key factors that mediate the aberrant cholesterol biosynthesis in
the advanced prostate cancers is urgently needed. This proposal is based on our recent discovery of a new
therapeutic target, namely a nuclear receptor protein RORgamma, for prostate cancer and evidence of our
further studies that suggest a possible direct role of the receptor protein and the cholesterol intermediates
in promoting the aberrant cholesterol synthesis in the prostate cancer tumor cells. Our preliminary results
also suggest that small-molecule inhibitors of the ROR can sensitize tumors to killing by statins. We
therefor wish to establish the novel function of the ROR protein in control of the aberrant cholesterol
synthesis in prostate cancer tumors, define its functional mechanisms and determine whether targeting the
receptor protein with a potent, prostate cancer-selective, small-molecule inhibitor, in combination with
statins, is a novel and highly efficacious therapeutic strategy for advanced prostate cancer.

## Key facts

- **NIH application ID:** 10084233
- **Project number:** 5I01BX004271-03
- **Recipient organization:** VA NORTHERN CALIFORNIA HEALTH CARE SYS
- **Principal Investigator:** Hongwu Chen
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10084233

## Citation

> US National Institutes of Health, RePORTER application 10084233, Therapeutic targeting of tumor metabolism in advanced prostate cancer (5I01BX004271-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10084233. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*