# Exploring DNA damage response pathways as targets for cancer therapy

> **NIH NIH R35** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2024 · $923,400

## Abstract

Project Summary:
It is well established that defects in DNA damage response (DDR) pathways accelerate tumorigenesis.
Significant efforts have been devoted to target defective DDR pathways to improve outcome for cancer patients.
These efforts led to the FDA’s approval of PARP inhibitors for the treatment of cancers carrying BRCA1/2
mutations and also the approval of immunotherapy for cancers with mismatch repair deficiency. Moreover, many
inhibitors targeting DNA repair and/or cell cycle checkpoints have also entered clinical trials. Thus, there is an
urgent need to understand how to effectively use these existing and new therapies for cancer treatment.
We now know that targeting DDR pathways and/or DDR defects not only affect intrinsic tumor proliferation, but
also change tumor-microenvironment interactions. Thus, we are expanding our DDR studies from in vitro to in
vivo settings. In this project, we will determine mechanistically how several essential DDR genes/proteins control
cell proliferation and DNA damage repair. We plan to establish separation of function mutations to further
elucidate the key roles of these DDR genes and pathways both in vitro and in vivo. Additionally, we will
investigate DDR defects in cancer therapy in vivo. Our recent success with in vivo CRISPR screens provides us
an opportunity to explore avenues to target DDR pathways and DDR defects for cancer treatment in vivo. We
anticipate that knowledge gained from these studies will help us design better treatment strategies for cancer
patients.

## Key facts

- **NIH application ID:** 10898051
- **Project number:** 5R35CA274234-03
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Junjie Chen
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $923,400
- **Award type:** 5
- **Project period:** 2022-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898051

## Citation

> US National Institutes of Health, RePORTER application 10898051, Exploring DNA damage response pathways as targets for cancer therapy (5R35CA274234-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10898051. Licensed CC0.

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