# Modulating dietary zinc to prevent cachexia and improve survival in cancer

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $370,575

## Abstract

ABSTRACT.
More than 80% of metastatic cancer patients experience a progressive and debilitating loss of muscle
mass and function by a process known as cachexia. Cachectic patients suffer deterioration of
diaphragm and cardiac muscles and often die prematurely due to respiratory and cardiac failure. The
prognosis for these patients is further diminished by the fact that they are often too weak to tolerate
standard doses of anti-cancer treatments. Our long-term goal is to identify and exploit the underlying
mechanisms that drive the development of cachexia to improve treatment response, survival and
quality of life in metastatic cancer patients. We recently identified a conserved mechanism of muscle
wasting in mice and patients with metastatic cancers in which the metal ion transporter, called
SLC39A14 (ZIP14), is upregulated in cachectic muscles (Wang et al., Nat Med, 2018). Muscle-
specific loss of ZIP14 alleviates the development of cachexia in these mouse models. Zinc is an
essential micronutrient that is often taken as a dietary supplement but in tumor bearing mice, excess
supplementation accelerates muscle wasting. In addition to cancer-induced cachexia, we now find
that certain chemotherapeutic drugs commonly used in patients (e.g. doxorubicin-cyclophosphamide
and cisplatin) can also cause Zip14 upregulation in the muscles of healthy mice and that Zip14 is
critical for chemotherapy-induced muscle atrophy in this context. Based on our preliminary studies,
our central hypothesis is that a subset of chemotherapeutic drugs perturbs metal-ion homeostasis
and promotes muscle wasting through the upregulation of Zip14 in muscle cells. Which chemotherapy
agents induce Zip14, how Zip14 is induced and the role of ZIP14 in chemotherapy-induced muscle
wasting remains to be explored. The proposed studies are expected to fill this gap and further our
understanding of the functions of ZIP14 in cancer- and chemotherapy-induced cachexia. Based on
our preliminary studies, in Aim 1, we will determine which chemotherapies promote muscle wasting
through the ZIP14 axis and whether Osteopontin, a candidate protein from serum profiling, regulates
chemotherapy-induced Zip14 expression in muscle cells. In Aim 2, we will develop strategies to
prevent chemotherapy-induced, Zip14-dependent muscle wasting in metastatic cancer models.
These studies could inform the development of new dietary intervention strategies to prevent or
reverse cachexia, with the aim of prolonging survival, improving treatment response and quality of life
in cancer patients with cachexia, in line with the objectives of the PQ11 and NCI.

## Key facts

- **NIH application ID:** 9899217
- **Project number:** 5R01CA231239-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Swarnali Acharyya
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $370,575
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899217

## Citation

> US National Institutes of Health, RePORTER application 9899217, Modulating dietary zinc to prevent cachexia and improve survival in cancer (5R01CA231239-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9899217. Licensed CC0.

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