# The paradoxical roles of beta hydroxy butyrate in the liver pro-metastatic niche

> **NIH NIH P01** · CEDARS-SINAI MEDICAL CENTER · 2023 · $140,891

## Abstract

Project Summary/Abstract
Liver metastasis is a steep obstacle for curative cancer treatment. Several cancers including prostate (PCa),
colorectal (CRC) and pancreatic ductal adenocarcinoma (PDAC) commonly metastasize to this site. Data shows
that liver metastasis is promoted by endocrine signaling from the primary tumor which can transform the liver
microenvironment. Nonetheless, this pre-metastatic to post-metastatic niche transformation can also be
influenced by therapy and diet. The ketogenic diet (KD) is a high-fat carb-restrictive diet that mimics fasting by
making fatty acids the main source of energy and promoting beta hydroxy butyrate (βHB) synthesis (ketosis).
KD has been successfully used to aid patients with neurodegenerative diseases. Additionally, it has been
proposed to ameliorate different types of cancer by inducing a reverse-Warburg effect and sensitizing cells to
checkpoint inhibitors. However, reports show that βHB enables adaptability to nutritional stress in cancer stem
cells and is associated with tumor progression and staging of prostate cancer. Nevertheless, βHB is also a
reported tumor suppressor being a known HDAC inhibitor and a signaling molecule through the niacin receptor,
GPR109a, in colon and breast cancer cells. Understanding that the liver is the main βHB synthesis organ, in this
study we aim to elucidate the effects of a ketogenic metabolism affecting the liver premetastatic niche and its
paradoxical roles with PCa and CRC in their distinct metabolic reprogramming.

## Key facts

- **NIH application ID:** 10745869
- **Project number:** 3P01CA233452-04S2
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Neil A. Bhowmick
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $140,891
- **Award type:** 3
- **Project period:** 2020-01-21 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10745869

## Citation

> US National Institutes of Health, RePORTER application 10745869, The paradoxical roles of beta hydroxy butyrate in the liver pro-metastatic niche (3P01CA233452-04S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10745869. Licensed CC0.

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