CHOP researchers are on a team getting up to $25 million to fight childhood cancers

A team that includes Children’s Hospital of Philadelphia researchers has been awarded up to $25 million to develop new treatments for stubborn childhood cancers that until now have been considered to be “undruggable.”

The team is one of five that will receive that amount of money from Cancer Grand Challenges, a program cofounded by the National Cancer Institute and Cancer Research UK.

The group with the CHOP researchers is tackling five childhood cancers that currently are treated mainly with chemotherapy and radiation, a blunt-force approach that kills healthy cells along with cancer cells. Such treatments have improved survival rates, but they can lead to toxic side effects that in turn can be life-threatening.

Instead, the team is developing drugs to degrade rogue proteins that are unique to these five cancers and not found in surrounding healthy cells.

The cancers the group is targeting include: neuroblastoma (nervous system), Ewing sarcoma (bone), fibrolamellar hepatocellular carcinoma (liver), medulloblastoma (brain), and rhabdomyosarcoma (various soft tissues).

Yael Mossé, a professor of pediatrics in the cancer center at CHOP, is the co-leader of the team, along with Martin Eilers at the University of Würzburg in Germany.

In a news release, Mossé said the team was “deeply honored” to have been picked from among 176 entrants.

“Each of the projects that applied for this funding were worthy, so we do not take this award lightly,” she said.

Other team members from CHOP include physicians John Maris and Adam Wolpaw.

In an interview, Wolpaw said the group will develop drugs that enhance the body’s ability to identify and dispose of cancerous proteins that feed the growth of tumors.

All cells are constantly in the process of degrading old proteins and replacing them with new ones. The type of drugs CHOP is studying would accelerate that process for the proteins involved in these cancers. Once these rogue proteins are cleared from a cancerous cell, it likely will die, Wolpaw said.

The group — named Team KOODAC³ (Knocking Out Oncogenic Drivers and Curing Childhood Cancer) — includes researchers from the U.S., Austria, France, Germany, and the United Kingdom.

They will test and develop the therapies in collaboration with Nurix Therapeutics, a San Francisco-basedbiotech firm that specializes in this emerging class of drugs, some of which are nicknamed “molecular glues.”

Among the four other award-winning teams is one that includes another CHOP researcher, Nikolaos G. Sgourakis That group, led by Michael Birnbaum at Massachusetts Institute of Technology, is studying how tumors are recognized by agents of the immune system called T-cells.

Each of the five groups stands to receive a total of $25 million over five years, pending annual progress reviews.