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多发性骨髓瘤的当代药物疗法。

Contemporary drug therapies for multiple myeloma.

作者信息

de la Puente P, Azab A K

机构信息

Department of Radiation Oncology, Cancer Biology Division, Washington University in Saint Louis School of Medicine, St. Louis, Missouri, USA.

出版信息

Drugs Today (Barc). 2013 Sep;49(9):563-73. doi: 10.1358/dot.2013.49.9.2020941.

Abstract

Multiple myeloma (MM) is an incurable disease characterized by the proliferation of plasma cells. The survival in MM patients has improved significantly in the past decade due to the introduction of novel agents. In this review, we focus on novel agents used in MM, including immunomodulatory drugs (thalidomide, lenalidomide and pomalidomide), proteasome inhibitors (bortezomib, carfilzomib, marizomib and ixazomib citrate), monoclonal antibodies (elotuzumab, siltuximab, daratumumab and BT-062), and drugs affecting an interaction with the tumor microenvironment (anti-VLA4 monoclonal antibody, chemokine CXCR4 inhibitor AMD-3100 and selectin inhibitor GMI-1070). We discuss their mechanism of action, preclinical and clinical outcome in the treatment of MM. Although the development of novel agents has improved the outcomes of MM treatment, most of the patients will still relapse and become refractory to therapy due to development of drug resistance. A better understanding of the biological mechanisms of MM progression, including cellular and molecular events in the MM cells and in their bone marrow microenvironment, is warranted to provide new therapeutic targets and develop new drugs and therapeutic strategies to treat MM.

摘要

多发性骨髓瘤(MM)是一种以浆细胞增殖为特征的不可治愈性疾病。在过去十年中,由于新型药物的引入,MM患者的生存率有了显著提高。在本综述中,我们重点关注MM中使用的新型药物,包括免疫调节药物(沙利度胺、来那度胺和泊马度胺)、蛋白酶体抑制剂(硼替佐米、卡非佐米、马立佐米和枸橼酸伊沙佐米)、单克隆抗体(埃罗妥珠单抗、西妥昔单抗、达雷妥尤单抗和BT - 062)以及影响与肿瘤微环境相互作用的药物(抗VLA4单克隆抗体、趋化因子CXCR4抑制剂AMD - 3100和选择素抑制剂GMI - 1070)。我们讨论它们在MM治疗中的作用机制、临床前和临床疗效。尽管新型药物的发展改善了MM治疗的结果,但由于耐药性的产生,大多数患者仍会复发并对治疗产生耐药。有必要更好地了解MM进展的生物学机制,包括MM细胞及其骨髓微环境中的细胞和分子事件,以提供新的治疗靶点并开发治疗MM的新药和治疗策略。

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