An interdisciplinary, global team of scientists led by Yael Mossé, MD, Professor of Pediatrics in the Cancer Center at Children’s Hospital of Philadelphia (CHOP), has been selected as one of five research teams from all over the world to receive funds from Cancer Grand Challenges, a funding initiative co-founded by the National Cancer Institute and Cancer Research UK. Mossé’s international team will receive up to $25 million to develop transformative new therapies for previously undruggable forms of childhood cancer.

Last year, 176 global teams submitted bold ideas for tackling some of the most pressing challenges in cancer research and care. Twelve teams were shortlisted, and the project “Developing a suite of oncoprotein degraders for childhood solid cancers,” nicknamed Team KOODAC3, emerged as one of five teams to receive funding after a year-long rigorous selection process. The team unites the expertise of researchers from the United States, Austria, France, Germany and the United Kingdom to tackle the challenge of oncogene-addicted solid tumors in children.

While survival rates for many childhood cancers have improved dramatically through the combination of standard chemotherapy and radiation therapy, survivors are often burdened with life threatening toxicities related to those therapies. Genetic discoveries related to cancer have transformed how many types of tumors are treated. Cancer is caused by genetic mutations that transform normal genes into oncogenes. These oncogenes are then translated into proteins that are not typically found in the cell, known as oncoproteins.

Several drugs have been developed to treat different tumors by targeting oncogenes and their associated oncoproteins. Despite advances in this field, a critical challenge has been the difficulty of targeting proteins responsible for causing solid tumors related to childhood cancers. As a result, cure rates for most solid tumors have not improved at the rate of other types of cancer.

KOODAC3 aims to develop drugs that break down or ‘degrade’ five of the most significant oncoproteins in children with high-risk oncogene-driven cancers, including neuroblastoma, medulloblastoma, Ewing sarcoma, fibrolamellar hepatocellular carcinoma, rhabdomyosarcoma and other cancers that deregulate these essential oncoproteins. The team is addressing this challenge by extending an ongoing collaboration with Nurix Therapeutics, a leading biopharmaceutical company focused on degrader drugs, providing a streamlined route for clinical translation of discoveries made by Team KOODAC3. Collectively, this consortium has the ambitious goal of developing oral drugs that will be deployed world-wide in partnership with a robust international patient advocacy committee that will inform outreach to childhood cancer communities globally.

“Our team is deeply honored to have been selected as one of the five to receive funding from the Cancer Grand Challenges initiative,” said Mossé. “Team KOODAC3 was brought together with the goal of identifying new strategies for treating high-risk pediatric cancers with a high unmet need. 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.”

Additional CHOP co-investigators who are part of Team KOODAC3 include John Maris, MD, and Adam Wolpaw, MD, PhD.

“At CHOP, our researchers are committed to creating life-changing solutions for children around the world, and improving the care for some of the most difficult to treat childhood cancers is what drives so much of what we do,” said Susan L. Furth, MD, PhD, Executive Vice President and Chief Scientific Officer at CHOP. “We are thrilled that this prestigious organization recognized the importance of what this project is trying to achieve, and we expect the funding to help us make important strides toward our understanding of childhood cancer.”

The National Cancer Institute and Cancer Research UK, the world’s leading funders of cancer research, co-founded and launched the Cancer Grand Challenges initiative in 2020. Cancer Grand Challenges aims to provide funding for interdisciplinary research teams from around the world whose novel ideas offer the greatest potential to advance bold cancer research and improve outcomes for people affected by cancer.

The team is co-led by Martin Eilers at the University of Würzburg in Germany and is funded by Cancer Research UK, Institut National Du Cancer and KiKa (Children Cancer Free Foundation) through Cancer Grand Challenges. Learn more about the Cancer Grand Challenges at https://cancergrandchallenges.org.

In addition to the Team KOODAC3 award, Team MATCHMAKERS, which includes Dr. Nikolaos G. Sgourakis from CHOP, also received a Cancer Grand Challenges award of up to $25 million.