Pancheri Elia, Guglielmi Valeria, Wilczynski Grzegorz M, Malatesta Manuela, Tonin Paola, Tomelleri Giuliano, Nowis Dominika, Vattemi Gaetano
Department of Neurosciences, Biomedicine and Movement Sciences, Section of Clinical Neurology, University of Verona, 37134 Verona, Italy.
Laboratory of Molecular and Systemic Neuromorphology, Department of Neurophysiology Warsaw, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland.
Cancers (Basel). 2020 Sep 7;12(9):2540. doi: 10.3390/cancers12092540.
The overall approach to the treatment of multiple myeloma (MM) has undergone several changes during the past decade. and proteasome inhibitors (PIs) including bortezomib, carfilzomib, and ixazomib have considerably improved the outcomes in affected patients. The first-in-class selective PI bortezomib has been initially approved for the refractory forms of the disease but has now become, in combination with other drugs, the backbone of the frontline therapy for newly diagnosed MM patients, as well as in the maintenance therapy and relapsed/refractory setting. Despite being among the most widely used and highly effective agents for MM, bortezomib can induce adverse events that potentially lead to early discontinuation of the therapy with negative effects on the quality of life and outcome of the patients. Although peripheral neuropathy and myelosuppression have been recognized as the most relevant bortezomib-related adverse effects, cardiac and skeletal muscle toxicities are relatively common in MM treated patients, but they have received much less attention. Here we review the neuromuscular and cardiovascular side effects of bortezomib. focusing on the molecular mechanisms underlying its toxicity. We also discuss our preliminary data on the effects of bortezomib on skeletal muscle tissue in mice receiving the drug.
在过去十年中，多发性骨髓瘤（MM）的总体治疗方法发生了几次变化。蛋白酶体抑制剂（PIs），包括硼替佐米、卡非佐米和伊沙佐米，显著改善了患病患者的治疗结果。一流的选择性蛋白酶体抑制剂硼替佐米最初被批准用于治疗该疾病的难治形式，但现在，与其他药物联合使用时，它已成为新诊断的MM患者一线治疗、维持治疗以及复发/难治性疾病治疗的基础用药。尽管硼替佐米是治疗MM最广泛使用且最有效的药物之一，但它可引发不良事件，这些不良事件可能导致治疗提前中断，对患者的生活质量和治疗结果产生负面影响。虽然周围神经病变和骨髓抑制已被公认为与硼替佐米最相关的不良反应，但心脏和骨骼肌毒性在接受治疗的MM患者中相对常见，但受到的关注要少得多。在此，我们综述硼替佐米的神经肌肉和心血管副作用，重点关注其毒性的分子机制。我们还讨论了关于硼替佐米对接受该药物治疗的小鼠骨骼肌组织影响的初步数据。
