# Targeting replication stress avoidance in cancer

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2021 · $467,554

## Abstract

Abstract
The overall goal of this proposal is to understand and target cancer cell addictions to stress- tolerance
pathways. We have discovered that cancer cells maintain proliferation by engaging in a pathway known as
translesion synthesis (TLS). By employing TLS, cancer cells are able to replicate in a continuous manner
and subvert the replication stress response. Here, we propose to implement state-of-the-art assays to
analyze how cancer cells alter DNA replication fork dynamics and replisome components to promote TLS.
By defining the core TLS machinery, we will seek to identify biomarkers and novel targets of TLS.
Importantly, we have developed a small molecule inhibitor of TLS that selectively halts DNA replication in
several cancer cell lines that are dependent on TLS. Moreover, we found that the colony forming potential of
TLS-dependent cancer cells is dramatically reduced upon inhibition of TLS. Thus, we propose to identify the
scope of TLS dependent cancers using cell screening and data base analysis. In addition, to fully further
develop the therapeutic potential of TLS inhibition, we propose to measure and improve the anti- cancer
potential of our lead small molecules. Collectively, these proposed studies will identify how cancer cells
engage TLS and how best to block TLS to selectively target cancer.

## Key facts

- **NIH application ID:** 10116341
- **Project number:** 5R01CA247232-02
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Sharon B Cantor
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $467,554
- **Award type:** 5
- **Project period:** 2020-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116341

## Citation

> US National Institutes of Health, RePORTER application 10116341, Targeting replication stress avoidance in cancer (5R01CA247232-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10116341. Licensed CC0.

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