# Targeting Atg5 in platinum-resistant ovarian cancer

> **NIH NIH R21** · WAYNE STATE UNIVERSITY · 2022 · $211,665

## Abstract

Abstract
Ovarian cancer is the fifth leading cause of cancer-related death in the United States. The standard first
line chemotherapy to treat this deadly disease includes platinum (cisplatin/carboplatin)-based treatment,
but the development of drug resistance presents a significant clinical problem that needs to be addressed.
Our current study identifies a novel mechanism of cisplatin resistance involving autophagy-related gene
(Atg) 5.
Atg5 is a member of the Atg family that plays an important role in regulating autophagy, a process
essential for the quality control of cellular components under various stress conditions. Previous studies
showed that the inhibition of autophagy sensitizes cancer cells to chemotherapy. Our own study showed
that the blockade of autophagy induction promotes cisplatin sensitivity in human ovarian cancer cells, but
strategies for targeting autophagy in cancer therapies in general are not well developed. We find that Atg5
is overexpressed in human ovarian tumors, and that its overexpression inhibits cisplatin-induced
apoptosis in ovarian cancer cells. We also find that Atg5 overexpression is correlated with the poor overall
survival in ovarian cancer patients treated with platinum-based chemotherapy. Additionally, we find that
Atg5 is phosphorylated but the effects of its phosphorylation on Atg5-mediated autophagy and cisplatin
resistance remain to be determined. Based on these novel observations, we hypothesize that elevated Atg5
expression confers growth advantage of ovarian cancer cells by promoting cell survival and drug
resistance. The objectives of this project are to define the role of Atg5 in cisplatin resistance and the
impact of Atg5 phosphorylation on cisplatin resistance. These objectives will be achieved by the following
two Specific Aims: 1) Define the role of Atg5 in cisplatin resistance both in vitro and in vivo using ovarian
cancer mouse models; and 2) Determine the regulation of Atg5 phosphorylation and its impact on
cisplatin resistance.
Successful results from this study could lead to the development of novel therapeutic strategies for
treating ovarian cancer patients.

## Key facts

- **NIH application ID:** 10307116
- **Project number:** 5R21CA249376-02
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** GEN SHENG WU
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $211,665
- **Award type:** 5
- **Project period:** 2021-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10307116

## Citation

> US National Institutes of Health, RePORTER application 10307116, Targeting Atg5 in platinum-resistant ovarian cancer (5R21CA249376-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10307116. Licensed CC0.

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