Will a New Drug That Stops Cell Repair Reduce Tumors in Children When Given With Chemotherapy?

Researchers at CHOP identified an enzyme that plays a key role in controlling the cell cycle a called checkpoint kinase or CHK1. The Wee1 inhibitor MK-1775 works with irinotecan to stop cell division and cause cell death. This combination drug treatment is being tested in children with neuroblastoma and medulloblastoma.

Project Title: Ph I/II MK-1775 Wee1 Inhibition + Irinotecan for Neuroblastoma and Medulloblastoma
Researcher: Kristina Cole, MD, PhD
Institution: Children’s Hospital of Philadelphia (CHOP)
Study Type: Phase I clinical trial
Status: Ongoing

Cancer cells multiply to form tumors and may travel to other parts of the body to form metastases. An important area of cancer research focuses on identifying where the cell cycle control is “broken” and interrupting that process with a targeted drug. Kinases are enzymes that have a major role in the control of the cell cycle, and scientists have discovered drugs to treat cancer by targeting these kinases. Researchers at CHOP identified an enzyme that plays a key role in controlling the cell cycle called checkpoint kinase or CHK1. By combining chemotherapy with inhibitors of these “repair proteins” (either CHK1 or Wee1) cancer cells become more sensitive to DNA damage induced by chemotherapy. The Wee1 inhibitor MK-1775 works with irinotecan to stop cell division and cause cell death. In this research project, this combination drug treatment is being tested in children with neuroblastoma and medulloblastoma with refractory or relapsed disease and is based on a previous preclinical study that was funded by Solving Kids’ Cancer.

To learn more about this trial, visit clinicaltrials.gov.