Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
Department of Pharmacy, Kyushu University Hospital, Fukuoka 812-8582, Japan.
Int J Mol Sci. 2021 Jan 17;22(2):888. doi: 10.3390/ijms22020888.
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.
硼替佐米是一种第一代蛋白酶体抑制剂，广泛用于血液恶性肿瘤的化疗，具有有效的抗癌活性，但常引起严重的周围神经病变。尽管硼替佐米引起的周围神经病变（BIPN）是一种剂量限制毒性，但目前尚无推荐的预防或治疗方法。其中一个最关键的问题是缺乏对 BIPN 病理机制的了解。在这里，我们根据临床前证据总结了 BIPN 的已知机制，包括形态异常、非神经元细胞的参与、氧化应激以及外周和中枢神经系统转录程序的改变。此外，我们还描述了有必要根据病理机制来确定已批准药物的潜在疗效的研究，因为这是一种将其快速转化为癌症和 BIPN 患者的有说服力的策略。
