Biomarker shines a light on new pathway to target neuroblastoma

A group of investigators at the prestigious Dana-Farber/Children's Hospital Cancer Center in Boston believe they may have identified the Achilles heel for a common malignant tumor found in pediatric oncology.

According to the scientists, the presence of MYCN amplification--a genetic biomarker linked to a poor patient prognosis--in tumors may mean that they are particularly sensitive to a new class of experimental cancer drugs known as BET bromodomain inhibitors. And that connection could be particularly important in the hunt for new drugs to attack neuroblastomas, the most common malignant tumor that threatens young children which are rich in MYCN proteins.

Kimberly Stegmaier, assistant professor of pediatrics in the Department of Hematology/Oncology at Dana-Farber/Children's Hospital Cancer Center, and her team reached that conclusion after screening more than 600 cancer cell lines with known genetic characteristics for sensitivity to a BET bromodomain inhibitor drug prototype. Using three animal models of MYCN-amplified neuroblastoma, the investigators found that their prototype drug reduced levels of MYCN in cells, making them more susceptible to cell death.

"Neuroblastoma is a devastating childhood cancer, and only a minority of children with high-risk disease will be cured with currently available treatments," Stegmaier said. "Prior research has shown that MYCN amplification is common in neuroblastoma, but it has been an elusive drug target."

The work could influence some key biotech players working in this sphere. Constellation Pharmaceuticals, for example, struck a pact with the Leukemia and Lymphoma Society last fall for work on small molecule BET bromodain inhibitors for hematologic malignancies. And other cancer drug developers may follow up as well.

- here's the press release