# Averting recurrent and resistant ovarian tumors

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2021 · $490,751

## Abstract

Tumor relapse and acquired chemotherapy resistance are two major factors leading to the high mortality of
epithelial ovarian cancer (EOC) patients. It has become increasingly evident that ovarian cancers contain
subpopulations of cancer stem cells (CSCs) with enhanced tumorigenicity and chemoresistance. These CSCs
are believed to be responsible for treatment failure and tumor relapse. However, it is still unclear how CSCs
survive DNA-damaging agent treatment, and how the tumor regenerated by the surviving CSCs develops
chemoresistance. Error-prone translesion DNA synthesis (TLS), a DNA damage tolerance mechanism that
bypasses DNA damage during replication, has been suggested to mediate acquired chemoresistance. Our
recent studies have revealed that ovarian CSCs show elevated expression of TLS polymerase η (Polη); we
also demonstrated that Polη is critical to the survival of ovarian CSCs following cisplatin treatment. Based on
this scientific premise, we generate a hypothesis that enhanced Polη-mediated TLS in CSCs contributes to
tumor relapse and the development of acquired cisplatin-resistance after initial cisplatin treatment, by
facilitating CSC survival and increasing CSC mutagenesis. The main objective of this proposal is to determine
a novel mechanism that contributes to EOC relapse and chemotherapeutic resistance following initial cisplatin
treatment. Two specific aims are proposed to test this hypothesis and achieve our goal. In specific aim 1, we
will determine the contribution of Polη-mediated TLS to EOC relapse after cisplatin treatment. In specific aim 2,
we will delineate the contribution of Polη-mediated TLS to the development of acquired cisplatin resistance in
the EOC and cisplatin-induced mutations in ovarian CSCs. The rationale under this proposal is that
understanding the mechanism underlying tumor relapse and chemotherapy resistance would facilitate the
development of new therapy strategies to improve the outcome of patients with EOC. It is our expectation that
at the conclusion of this project, we will have provided solid evidence showing that enhanced expression of
Polη in ovarian CSCs contributes to the tumor regrowth, mutagenesis in CSCs, and the development of
cisplatin resistance after initial cisplatin treatment. Downregulation of Polη would significantly inhibit tumor
relapse and prevent the development of cisplatin resistance, and thus, can be exploited for a new therapy
strategy for EOCs.

## Key facts

- **NIH application ID:** 10058817
- **Project number:** 5R01CA211175-05
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Qien Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $490,751
- **Award type:** 5
- **Project period:** 2016-12-19 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10058817

## Citation

> US National Institutes of Health, RePORTER application 10058817, Averting recurrent and resistant ovarian tumors (5R01CA211175-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10058817. Licensed CC0.

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