The molecular and cellular insight into the toxicology of bortezomib-induced peripheral neuropathy

The proteasome inhibitor bortezomib (BTZ) is a first-line antitumor drug, mainly used for multiple myeloma treatment. However, BTZ shows prominent toxicity in the peripheral nervous system, termed BTZ-induced peripheral neuropathy (BIPN). BIPN is characterized by neuropathic pain, resulting in a dose reduction or even treatment withdrawal. To date, the pathological mechanism of BIPN has not been elucidated. There is still no effective strategy to prevent or treat BIPN. This review summarizes the pathological mechanisms of BIPN, which involves the pathological changes of Schwann cells, neurons, astrocytes and macrophages. A better knowledge of the pathological mechanisms of BIPN would provide new ideas for therapeutic interventions of BIPN patients. [Display omitted] •BTZ damaged Schwann cells, leading to demyelination, aggregates formation, ER stress and dedifferentiation inhibition.•BTZ caused neuronal dysfunction, including hyperexcitability, abnormality of subcellular structure and neuroinflammation.•The astrocytes activated by BTZ mediate the imbalance of glutamate release and reuptake, resulting in neuropathic pain.•The macrophage infiltration caused by BTZ is related to the development of neuropathic pain.