# Targeting circulating HSP70 and HSP90 for the treatment of cancer cachexia

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2021 · $166,452

## Abstract

Summary
Cachexia, characterized by muscle wasting, is a lethal complication of cancer seen in more than 50% of
cancer patients and the immediate cause of ~30% cancer related death. However, due to the poor
understanding of its highly complex etiology, there has been no FDA-approved treatment for cancer cachexia.
We recently discovered in mouse cancer models that cancer cell-released circulating HSP70 and HSP90
associated with exosome-type extracellular vesicles (EV) are key inducers of muscle wasting by activating
TLR4 on skeletal muscle cells. In addition, elevated circulating HSP70/90 are responsible for the elevation of
such catabolic cytokines as TNFa and IL-6 due to their systemic activation of TLR4. These data suggest that
elevated circulating HSP70/90 are key inducers of inflammation and muscle wasting, which are the primary
features of cancer cachexia. Thus, targeting cancer cell-released EV-associated HSP70 and HSP90 could be
an effective therapeutic strategy for cancer cachexia. However, animal models do not always recapitulate
complex events that occur in cancer cachexia in humans, it will be important moving forward to verify the roles
of elevated circulating HSP70 and HSP90 in human cancer cachexia, which is hindered by the lack of tools to
intercept circulating HSP70 and HSP90 in humans. In this R21 application, we propose to test the hypothesis
that elevated circulating HSP70 and HSP90 are key inducers of muscle wasting in human cancer cachexia by
generating neutralizing antibodies against human HSP70 and HSP90 with high efficacy, specificity, and
defined epitopes, and determining whether the antibodies ameliorate muscle wasting in in vitro and in vivo
models of human cancer cachexia. If successful, these antibodies can be used in future clinical studies to
determine whether intercepting elevated circulating HSP70 and HSP90 ameliorates muscle wasting in cancer
patients.

## Key facts

- **NIH application ID:** 10212970
- **Project number:** 5R21AR076699-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** YI-PING LI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $166,452
- **Award type:** 5
- **Project period:** 2020-07-08 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212970

## Citation

> US National Institutes of Health, RePORTER application 10212970, Targeting circulating HSP70 and HSP90 for the treatment of cancer cachexia (5R21AR076699-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10212970. Licensed CC0.

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