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

Abstract

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.