Childhood Cancer

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Stapled Peptide PROTAC: A 3-in-1 Treatment for Pediatric Solid Tumors

Dana-Farber Cancer Institute
Loren Walensky, MD/PhD
Grant Type: 
Reach Grants
Year Awarded: 
Type of Childhood Cancer: 
Ewing Sarcoma, Neuroblastoma, Osteosarcoma
Project Description: 

Cancer is the leading cause of death by a disease in children ages 0-19 years old. Whereas cure rates for pediatric hematologic malignancies as a class can reach 90% or more, solid tumor cures have historically lagged and contribute disproportionately to the cancer death rate in children. A common mechanism among relapsed and treatment-resistant pediatric solid tumors is a combination of errant signaling that drives cancer cell proliferation and blocks cancer cell death. Thus, multiagent treatment that addresses multiple cancer-causing pathways is required. However, advancing new anti-cancer drug candidates, especially in combination, is especially challenging in children. First, concerns about unanticipated toxicities have long led regulators to require clinical testing in adults before children, causing considerable delays in initiating Phase 1 trials in pediatric cancer. Second, new agents must initially show safety and activity as a single agent before being applied in combination. Third, identifying effective combinations and then brokering clinical testing agreements that bring companies and their proprietary drugs together remains a formidable, logistical barrier. Finally, individual drugs have distinct properties that from a practical standpoint can thwart the delivery of both agents to the same cancer cell at the same time. Here, we combine two technologies to create a single drug that can simultaneously target three key cancer-causing mechanisms of pediatric solid tumors, effectively overcoming major barriers to clinical translation.