# Adipokine Signaling as a Therapeutically Targetable Driver of Tumor Metabolism

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2024 · $341,057

## Abstract

Project Summary:
The link between obesity and cancer is well-established epidemiologically, but poorly understood at a
mechanistic level. Clear cell renal cell carcinoma (ccRCC) is the most common form of renal cancer, and has
clear ties with metabolic syndrome. ccRCC simultaneously demonstrates drastic metabolic rewiring at the
histological and molecular levels that recently have been found to be essential for tumor development.
Currently, however, the standard of care for ccRCC is targeted therapeutics against tyrosine kinases including
the VEGF receptor, that in most cases lead to modest improvements in overall survival. Thus identification of
new approaches to treat ccRCC is needed, and altered metabolism may offer a clinically useful foothold. We
have investigated the characteristic lipid storage phenotype of ccRCC and identified a molecular mechanism
that is driven in part by obesity. The present application focusses on a soluble adipokine produced by fat and
tumors that suppresses lipid catabolism, and is essential for tumor growth. The very nature of a secreted
factor leads to both diagnostic and therapeutic potential, and here we investigate the impact of inhibiting the
adipokine, Chemerin, with multiple approaches including a monoclonal antibody in preclinical animal models of
ccRCC, and a genetically engineered mouse model (GEMM). We will also dissect the mechanisms of action of
Chemerin on tumor and non-tumor cells, and examine the significance of Chemerin isoforms in collected
clinical specimens. Together, the aim of the proposal is to validate a novel target in ccRCC that could be
combined with existing therapies to improve patient outcomes.

## Key facts

- **NIH application ID:** 10786126
- **Project number:** 5R01CA254409-04
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Scott Michael Welford
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $341,057
- **Award type:** 5
- **Project period:** 2021-03-05 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10786126

## Citation

> US National Institutes of Health, RePORTER application 10786126, Adipokine Signaling as a Therapeutically Targetable Driver of Tumor Metabolism (5R01CA254409-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10786126. Licensed CC0.

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