How p53 Mutations Drive Cancer and How USP7 PROTAC Could Block Them
Official title: Mechanisms of the Gain-of-functions of p53 mutants and the effects by USP7 PROTAC
Funded at Icahn School of Medicine at Mount Sinai · NIH-11378643 · Data updated 2026-11-12
A cancer research program is exploring how mutant p53 proteins promote tumor growth and spread, and whether a drug called USP7 PROTAC can lower those mutant proteins to slow cancer.
Quick facts
| Grant type | P01 program project |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Icahn School of Medicine at Mount Sinai NIH-funded |
| Lab location | 1 site (New York, United States) |
| Project start | August 1, 2025 |
| Project end | July 31, 2030 |
| Funding year | 2026 |
| Award (this year) | $608,551 |
| NIH project number | 5P01CA291694-02 |
| Project ID | NIH-11378643 on NIH RePORTER |
Who could benefit from this research
✓Could help
Patients whose cancers harbor p53 missense mutations, particularly those with the p53 R175H variant, may benefit from the insights or future therapies arising from this work.
✕Less likely to help
Patients whose tumors do not involve p53 mutations or who are not eligible for trials based on other criteria may see no direct benefit.
What this research studies
This project focuses on different mutant forms of p53, which are common in many cancers, and how they gain features that help tumors grow and metastasize. Scientists are studying how a protein called BACH1 interacts specifically with certain p53 mutants to influence cell survival and cancer progression, and how USP7 controls the stability of the mutant p53 protein. They will test a small-molecule degrader (USP7 PROTAC) to reduce the levels of problematic p53 mutants and observe effects on tumor behavior. The work uses cell lines and other biochemical approaches to understand the mechanisms driving cancer and to identify potential therapeutic strategies. The grant supports a multi-year effort at a leading cancer research center to translate mechanistic insights into potential treatments.
Why it matters
Potential benefit: If successful, this research could lead to new ways to slow or stop cancers driven by specific p53 mutations by degrading the mutant proteins.
How similar studies have gone: Previous studies have shown that targeting mutant p53 pathways can influence tumor behavior, supporting the potential of this approach, though the exact USP7 degrader strategy is being explored.
Where this research is happening
-
Icahn School of Medicine at Mount Sinai
New York, United States Active
Researchers
- Principal investigator: Manfredi, James J — Icahn School of Medicine at Mount Sinai
- Study coordinator: Manfredi, James J
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About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.