A global team of scientists led by a Children's Hospital of Philadelphia doctor was one of five groups selected to receive a multimillion-dollar grant from Cancer Grand Challenges, a funding initiative co-founded by the National Cancer Institute and Cancer Research UK.

The international team headed by Dr. Yael Mossé, a professor of pediatrics in the cancer center at CHOP, will receive up to $25 million to develop "transformative" therapies for previously undruggable forms of childhood cancer.

Their application was among 176 submitted for funding.

Mossé's group, nicknamed Team KOODAC3, consists of researchers from the United States, Austria, France, Germany and the United Kingdom. CHOP researchers Dr. John Maris and Dr. Adam Wolpaw are co-investigators with Team KOODAC3 — an acronym for Knocking Out Oncogenic Drivers and Curing Childhood Cancer. Collectively they are working to tackle the challenge of oncogene-addicted solid tumors in children.

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CHOP

The team's focus is on developing a suite of oncoprotein degraders for childhood solid cancers. Oncoproteins are the core components of the body's signaling pathways that regulate cell growth, division and proliferation.

Specifically, Team KOODAC3 intends to develop drugs that break down or degrade five of the most significant oncoproteins in children with high-risk oncogene-driven cancers such as neuroblastoma, medulloblastoma, Ewing sarcoma, fibrolamellar hepatocellular carcinoma, and rhabdomyosarcoma.

“Team KOODAC3 was brought together with the goal of identifying new strategies for treating high-risk pediatric cancers with a high unmet need," Mossé said. "Each of the projects that applied for this funding were worthy, so we do not take this award lightly and we are committed to bringing our expertise together with the goal of developing paradigm-altering safe and effective new therapies for currently lethal childhood solid cancers.”

CHOP officials noted cancer is caused by genetic mutations that transform normal genes into oncogenes, which are genes that have the potential to cause cancer. Such oncogenes are then translated into oncoproteins, which proteins that are not typically found in the cell. While several drugs have been developed to treat different tumors by targeting oncogenes and their associated oncoproteins, developing drugs that target proteins responsible for causing solid tumors related to childhood cancers has proven to be elusive.

The KOODAC3 team is addressing this challenge by extending an ongoing collaboration with Nurix Therapeutics, a San Francisco biopharmaceutical company focused on degrader drugs.

The National Cancer Institute and Cancer Research UK co-founded and launched the Cancer Grand Challenges initiative in 2020 with a mission of providing funding for interdisciplinary research teams from around the world whose novel ideas offer the greatest potential to advance cancer research and improve outcomes for people affected by cancer.

Author: John George

Publication: Philadelphia Business Journal

Link: CHOP doctor-led international research team wins $25M grant - Philadelphia Business Journal (bizjournals.com)