Fall 2025
By Kathy Clute
Photography by Sam Ogden
Dana-Farber has been awarded more than $3 million in funding as part of a Cancer Grand Challenge to find new treatments for solid tumors in children. “Outcomes for some pediatric cancers have not improved in more than 30 years,” said David Scott, PhD, director of Cancer Grand Challenges.
“Standard treatment regimens continue to rely on cytotoxic agents and, often, radiotherapy, which induce an alarming rate of severe health effects later in life.”
In 2025, about 15,000 U.S. children and adolescents ages birth to 19 are expected to be diagnosed with cancer, according to the American Cancer Society. Solid tumors, which include brain tumors, neuroblastoma, and others, make up a significant portion of these cases.
The Dana-Farber faculty members working on the Grand Challenge are part of a collaborative, international team called PROTECT—Harnessing PROTEin Degradation for Advanced Childhood Tumors. Protein degraders are an emerging class of therapeutic agents designed to target and eliminate specific proteins within cancer cells. Kimberly Stegmaier, MD, is leading the Dana-Farber contingent, which includes Scott Armstrong, MD, PhD, the Ted Williams Chair at Dana-Farber; Cigall Kadoch, PhD, the Meredith and Billy Starr Investigator at Dana-Farber; Eric Fischer, PhD, the Joseph Deitch Family Chair at Dana-Farber; and Dana-Farber President and CEO Benjamin L. Ebert, MD, PhD, the Richard and Susan Smith Professor of Medicine at Harvard Medical School. Stegmair is the David G. Nathan, MD, Professor of Pediatrics at Harvard Medical School as well as chair of the Pediatric Oncology Department. Team PROTECT is led by Stefan Pfister, MD, from the German Cancer Research Center/DKFZ in Germany, uniting clinicians, advocates, and scientists across 10 institutions and five countries.
“Cures will require innovative interventions that specifically target the unique biology of pediatric tumors,” Stegmaier said. “Our goal is to develop a new generation of therapeutic approaches for children with Ewing sarcoma, neuroblastoma, synovial sarcoma, rhabdomyosarcoma, ependymoma, and high-grade glioma by targeting proteins previously thought to be undruggable.”
The team is developing small molecule prototype drugs that work by bringing together proteins expressed in the cancer cells and a special enzyme called an E3 ligase. This enzyme targets the protein for destruction, allowing the cell to dispose of it.
The goal is to advance the most promising project to the point where an Investigational New Drug (IND) application can be filed with the U.S. Food and Drug Administration, demonstrating that a drug is reasonably safe for initial testing in humans. If the IND application is approved, Phase 1 clinical trials can begin.
Cancer Grand Challenges is a global research initiative that identifies the toughest challenges in cancer research. Team PROTECT is funded by Cancer Research UK, the National Cancer Institute, The Spanish Association Against Cancer, and KiKa (Children Cancer Free Foundation).