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In recent years, the complexity of cancer and cancer therapies and their interactions with the peripheral nervous system have come into focus, but limitations in experimental models have remained a significant challenge in the field. As evidence, there are currently no therapies approved that target cancer-peripheral nervous system or cancer therapy-peripheral nervous system interactions as an anti-neoplastic or anti-neurotoxic agent, respectively. Human pluripotent stem cells offer an appealing model system that, unlike rodent models, is compatible with high throughput, high content applications; techniques that reflect modern drug discovery methodologies. Thus, utilizing the key advantages of stem cell-based models in tandem with the strengths of traditional animal models offers a complementary and interdisciplinary strategy to advance cancer and cancer therapy-peripheral nervous system research and drug discovery. In this review, the current status of the cancer-peripheral nervous system and cancer therapy-peripheral nervous system research is discussed, examples where stem cell-based models have been implemented are described, and avenues where stem cell-based models may further advance the field are proposed.

Neural crest (NC) cells are migratory multipotent progenitors that delaminate from the neural tube during embryonic development and give rise to various cell types in different organs. These cells are a transient embryonic cell population and therefore difficult to obtain from primary sources. Deriving NC from human pluripotent stem cells offers an alternative way to provide large-scale human NC cells for developmental and disease-related studies. In recent years, the protocols to make these cells have matured, incorporating the efficient conversion of pluripotent stem cells to neural cells through dual SMAD inhibition and early Wnt activation to increase the yield of NC cells. Here, we provide a minor variation to this NC protocol that has been successful for many in our laboratories.