A targeted approach for p53‑mutant colorectal cancer
Novel synthetic lethality strategy for TP53 mutant colorectal cancer
Seeks to kill colorectal tumors with p53 (TP53) mutations by pairing a DNA‑damaging thymidine analogue with drugs that block DNA repair (PARP inhibitors).
Quick facts
| Grant type | R37 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Roswell Park Cancer Institute Corp NIH-funded |
| Lab location | 1 site (Buffalo, United States) |
| Project ID | NIH-11159493 on NIH RePORTER |
What this research studies
If your colorectal tumor has a TP53 (p53) mutation, researchers are testing a two‑step approach that first causes DNA damage by inserting a thymidine analogue into tumor DNA and then blocks the tumor’s repair machinery with PARP inhibitors so the cancer cells die. This work builds on lab and animal studies showing p53‑deficient cells accumulate damaging breaks when treated this way. The team validated the concept across multiple preclinical models and aims to move it closer to patient testing. The focus is on treatments that more selectively target p53‑mutant tumors to limit harm to normal tissues.
Who could benefit from this research
Good fit: People with colorectal adenocarcinoma whose tumors have confirmed TP53 (p53) mutations, especially those with advanced or treatment‑resistant disease, would be the most likely candidates.
Not a fit: Patients whose tumors retain normal (wild‑type) p53 or who have non‑colorectal cancers are unlikely to benefit from this specific approach.
Why it matters
Potential benefit: Could offer a more selective and potentially less toxic treatment option for patients with p53‑mutant colorectal cancer.
How similar studies have performed: The combination idea uses FDA‑approved drug components and PARP inhibitors and has strong support from preclinical studies, but it has not yet been proven effective in patients for this specific strategy.
Where this research is happening
Buffalo, United States
- Roswell Park Cancer Institute Corp — Buffalo, United States (Active)
Researchers
- Principal investigator: Fountzilas, Christos — Roswell Park Cancer Institute Corp
- Study coordinator: Fountzilas, Christos
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 below.