Paediatric Therapeutic Development Workshop on rhabdomyosarcoma

Area of Science:

• Pediatric Oncology
• Cancer Therapeutics
• Molecular Biology

Background:

• Rhabdomyosarcoma is the most common pediatric soft tissue sarcoma.
• Survival rates vary significantly based on disease risk, with metastatic disease having poor outcomes (20-30%).
• There is an urgent need for novel therapeutics targeting high-risk rhabdomyosarcoma and reducing treatment toxicity.

Purpose of the Study:

• To identify and prioritize key therapeutic targets and strategies for rhabdomyosarcoma.
• To guide future preclinical and clinical development of novel treatments.
• To address the unmet need for effective therapies in high-risk and metastatic rhabdomyosarcoma.

Main Methods:

• Review and discussion of emerging therapeutic targets and approaches.
• Identification of priority targets including FGFR4, PAX3/7::FOXO1 fusion proteins, MYOD1, P300/CBP, TEAD, and B7-H3/CD276.
• Consideration of drug combinations, including MEK, BRAF, PI3K inhibitors, and Notch inhibitors.

Main Results:

• Several high-priority targets for therapeutic development were identified, including FGFR4, PAX3/7::FOXO1, MYOD1, TEAD, and B7-H3/CD276.
• Specific strategies like degraders (FGFR4, MYOD1, TEAD, P300/CBP) and antibody-drug conjugates (B7-H3/CD276) show promise.
• Combinatorial approaches involving MEK inhibitors with other agents are recommended for evaluation.

Conclusions:

• Targeted therapies and drug degraders represent promising avenues for rhabdomyosarcoma treatment.
• Further preclinical evaluation and optimized clinical trial design are essential for advancing these therapies.
• Addressing high-risk and metastatic disease requires innovative therapeutic strategies and combination approaches.