Preventive Strategies for Chemotherapy-Induced Peripheral Neuropathy: Basic Science and Models for Drug Development

There are no clinically relevant, evidence-based preventive strategies for chemotherapy-induced peripheral neuropathy (CIPN). In this chapter we discuss how limitations in current animal models lead to insufficient understanding of CIPN pathophysiology and how drug development for neurodegenerative diseases in general suffers because of this. We draw on previous studies of CIPN prevention to reflect upon what can be learned, but this chapter is not a historical account of past CIPN strategies nor it is an exhaustive list of CIPN mechanisms in rodents and mice. There are several succinctly well-written and recent reviews that cover these topics.

We look towards the horizon of CIPN drug development and provide an overview of the strategies that are emerging. We argue that some of these strategies herald early signs of methodological change for CIPN research, where basic science researchers begin to employ a systems biology approach to model neurological diseases such as CIPN in greater pathophysiological detail. Here diseases are caused by disruption to biological networks such as the neuron/neuroglia homeostasis rather than singular mechanisms within individual cell types. In this new perspective, we suggest three “core mechanisms” of CIPN that could be modeled within a systems biology methodology. We present studies that show how new methods, such as single cell multi-omics and bioengineering of human 3D organoids, can be analyzed with machine learning algorithms to aid CIPN drug development.