# Novel therapeutics for targeting checkpoint dysfunction in cancer

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $362,569

## Abstract

Proper checkpoint activation is necessary to temporarily halt cell cycle progression when
cells are in nutrient-deprived conditions or encounter insults. These safeguard
mechanisms are universally lost in cancer cells; nevertheless, some causes for the
checkpoint perturbation in cancer remain to be investigated. In addition, it remains a
challenge to translate our knowledge in this field into practical cancer therapy. The main
goal of this project is to develop novel therapeutics aiming at cancer checkpoint
perturbation. In this proposal, first we will study how certain hotspot mutations of tumor
suppressor p53 actively inhibit the checkpoint response. Second, we will determine
whether some mutant p53 directly promotes DNA replication, and if so, by what
mechanism(s). Third, we will identify small molecule inhibitors targeting these molecular
events. Lastly, we propose a “synthetic targeted therapy” strategy and leverage our new
findings with the existing knowledge for cancer therapy. In our preliminary study, we
have identified several lead inhibitors targeting this event. With the aid of one lead
inhibitor we have obtained proof-of-concept to support feasibility of the proposed
concept. In short, the proposed study will elucidate novel mechanisms of checkpoint
perturbation and translate our discoveries into new therapeutics for a broad range of
cancers.

## Key facts

- **NIH application ID:** 9825532
- **Project number:** 5R01CA203824-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** FANG-TSYR LIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $362,569
- **Award type:** 5
- **Project period:** 2016-12-15 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9825532

## Citation

> US National Institutes of Health, RePORTER application 9825532, Novel therapeutics for targeting checkpoint dysfunction in cancer (5R01CA203824-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9825532. Licensed CC0.

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