Internal medicine

Pathological

Diabetes mellitus

Cancer

Endocrinology

Oncology

Multiple myeloma

Immunology

Proteasome inhibitor

Malignancy

Bortezomib

Peripheral neuropathy

Medicine

International Journal of Molecular Sciences

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.

Pathological Mechanisms of Bortezomib-Induced Peripheral Neuropathy