Peripheral nerve sheath tumors-on-a-chip: Next-generation platforms for mechanistic and therapeutic studies

Recapitulation of the complex nerve–tumor–immune microenvironment is critical for understanding Peripheral Nerve Sheath Tumors (PNSTs). Conventional in vitro models and animal systems often struggle to model crucial intercellular and inter-organ communication with full physiological relevance, creating a bottleneck in discovering effective therapeutics. Organ-on-Chip (OoC) technologies offer a paradigm-shifting solution. These microengineered platforms precisely integrate human cell biology with controllable fluidic and mechanical cues to replicate tissue- and organ-level physiology, enabling real-time, quantitative monitoring of tissue dynamics. This review posits that OoC technology is poised to revolutionize PNST research. In this review, we summarize the development of advanced Tumor-Nerve-Immune-on-Chip systems that integrate patient-derived Schwann cells, immune components, and functional microvasculature. These systems will accurately model PNSTs. Adoption of OoC will enable a predictive and individualized experimental framework, accelerating therapeutic discovery and allowing for personalized drug prediction for these challenging diseases. • Defining the specific requirements and design space of next-gen PNST-on-chip platforms. • Organ-on-Chip technology mimics complex human nerve tumor environments. • Patient-specific models accelerate personalized drug discovery.