Bortezomib, a first-generation proteasome inhibitor widely used in chemotherapy for hematologic malignancy, has effective anti-cancer activity but often causes severe peripheral neuropathy. Although bortezomib-induced peripheral neuropathy (BIPN) is a dose-limiting toxicity, there are no recommended therapeutics for its prevention or treatment. One of the most critical problems is a lack of knowledge about pathological mechanisms of BIPN. Here, we summarize the known mechanisms of BIPN based on preclinical evidence, including morphological abnormalities, involvement of non-neuronal cells, oxidative stress, and alterations of transcriptional programs in both the peripheral and central nervous systems. Moreover, we describe the necessity of advancing studies that identify the potential efficacy of approved drugs on the basis of pathological mechanisms, as this is a convincing strategy for rapid translation to patients with cancer and BIPN.
Keywords: bortezomib; drug repositioning; drug repurposing; neuropathic pain; neurotoxicity; peripheral neuropathy.