Advances in Targeting Growth Factor Signalling in Neuroblastoma and Overcoming Drug Resistance

Area of Science:

• Pediatric Oncology
• Developmental Biology
• Cancer Signaling

Background:

• Neuroblastoma originates from neural crest cells and is a leading cause of childhood cancer mortality.
• Growth factor signaling is crucial for neural crest development and often remains dysregulated in neuroblastoma.
• Receptor tyrosine kinase (RTK) inhibitors offer a targeted approach, but resistance is a significant challenge.

Purpose of the Study:

• To review the role of growth factor receptors in neural crest and neuroblastoma development.
• To systematically overview RTK inhibitors for neuroblastoma and their clinical status.
• To explore resistance mechanisms and strategies for combination therapies.

Main Methods:

• Literature review of single-cell studies on neural crest and neuroblastoma.
• Systematic analysis of RTK inhibitors in clinical development for neuroblastoma.
• Exploration of intratumoral heterogeneity and resistance mechanisms like adrenergic-to-mesenchymal transition.

Main Results:

• Growth factor signaling pathways are key drivers in neuroblastoma, offering therapeutic targets.
• Intratumoral heterogeneity, particularly the adrenergic-to-mesenchymal transition, contributes to resistance against RTK inhibitors.
• Current RTK inhibitors show variable efficacy, often necessitating combination strategies.

Conclusions:

• Targeting growth factor receptor signaling with RTK inhibitors is a promising strategy for neuroblastoma.
• Overcoming resistance requires addressing tumor cell plasticity and escape mechanisms.
• Combination therapies hold potential for improving outcomes in high-risk neuroblastoma.