Killing p53-deficient cancers by boosting harmful oxygen and blocking DNA repair
Simultaneous ROS production and DDR inhibition to trigger p53 synthetic lethality
New drugs that raise damaging oxygen levels and block DNA repair are being developed to kill cancers that lack a working p53 gene.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Children's Mercy Hosp (Kansas City, Mo) NIH-funded |
| Lab location | 1 site (Kansas City, United States) |
| Project ID | NIH-11301006 on NIH RePORTER |
What this research studies
Researchers aim to create compounds that both increase reactive oxygen species (ROS) and inhibit the DNA damage response so cells missing p53 selectively die. They discovered a compound called KU that kills p53-deleted or mutated cancer cells while sparing normal cells, and have stronger KU analogs named KU-D2 and KU-D2F. The project will test these compounds in laboratory cancer models, study how they cause mitotic arrest and DNA damage, and optimize them for stronger, more specific activity. The ultimate goal is to turn these findings into therapies that target p53-deficient tumors with fewer side effects.
Who could benefit from this research
Good fit: Patients whose tumors have p53 mutations or deletions—such as certain osteosarcomas and many other cancers—would be the intended candidates for these therapies.
Not a fit: Patients whose cancers have intact, functional p53 or whose disease is driven by other mechanisms are unlikely to benefit from this specific approach.
Why it matters
Potential benefit: If successful, this approach could produce treatments that selectively kill p53-deficient tumors while reducing harm to normal tissues.
How similar studies have performed: Related lab studies have shown promise but similar compounds have not yet proven effective in clinical trials, so the approach remains experimental.
Where this research is happening
Kansas City, United States
- Children's Mercy Hosp (Kansas City, Mo) — Kansas City, United States (Active)
Researchers
- Principal investigator: Iwakuma, Tomoo — Children's Mercy Hosp (Kansas City, Mo)
- Study coordinator: Iwakuma, Tomoo
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.