Tomoo Iwakuma, MD, PhD

Director, Translational Hematology Oncology Research; Co-Leader, Cancer Biology Program, University of Kansas Cancer Center; Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Research Professor of Cancer Biology, University of Kansas School of Medicine

Full Biography

Tomoo Iwakuma, MD, PhD, Hematology/Oncology/BMT, received a $2,743,290 R01 grant from the National Institutes of Health’s National Cancer Institute. The grant is for his study, “Simultaneous ROS production and DDR inhibition to trigger p53 synthetic lethality” and covers a project period of March 11, 2025-February 28, 2030 (Award Number: 1R01CA285616-01A1).

The study aims to find new ways and compounds to kill cancer cells that don’t have a normal p53 gene, which is found in about 50 percent of human cancers.

Previous compounds that target these cells haven't worked well and aren't used in hospitals because scientists don't yet fully understand how they work, they only work in certain situations, and they currently aren't very effective. Since these compounds don't harm normal cells with a working p53 gene, Dr. Iwakuma’s study will help create a new treatment with fewer side effects, improving life for cancer patients and benefiting public health.

The study team’s recent tests found a compound called "KU" that can damage DNA, stop cell division, and kill cancer cells in bone cancer (osteosarcoma) that don't have a normal p53 gene. "KU" doesn't harm normal cells with a working p53 gene. It causes the production of harmful molecules called reactive oxygen species (ROS) and blocks a protein called ATM from working. They also found that modified versions of KU are even better at killing these cancer cells and are more specific to cells without p53.

The study will find out if creating DNA damage and blocking DNA repair, by producing reactive oxygen species and simultaneously inhibiting the corresponding damage repair signaling, can effectively kill cancer cells without a normal p53 gene, similar to how KU compounds work. The team will also identify which proteins bind to KU compounds and cause these effects.

Dr. Iwakuma and his team will then test the safety and effectiveness of the modified versions of KU. They’ll see if these compounds can shrink tumors and if using both a reactive oxygen species inducer and an ATM blocker can stop the growth of tumors without p53, like the KU compound does.

“This study will show that cancer cells without p53 are vulnerable to simultaneous treatments that cause DNA damage and block the corresponding DNA repair signaling. We'll also find new compounds that can kill these cancer cells on their own, which could lead to new cancer treatments,” explains Dr. Iwakuma.

Co-investigators include Stefan Bossmann, PhD, KUMC; Whitney Nolte, PhD, Clinical Pharmacology; and Hung-Wen Yeh, PhD, Health Services and Outcomes Research, both of Children’s Mercy.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.