New strategies in the treatment of multiple myeloma.
New strategies in the treatment of multiple myeloma.
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DOI：
10.1158/1078-0432.ccr-12-1881
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发表时间：
2013-07-01
期刊：
影响因子：
--
通讯作者：
Anderson KC
中科院分区：
文献类型：
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作者：
Munshi NC;Anderson KC
多发性骨髓瘤（MM）是影响终末分化浆细胞的第二大常见血液恶性肿瘤。尽管高剂量化疗和自体干细胞移植改善了年轻患者的生存率，但MM的自然史已随着过去10年中批准的5种新药（沙利度胺、硼替佐米、来那度胺、脂质体阿霉素和卡非佐米）的可用性而改变。尽管总体结局显著改善，但大多数患者的MM仍无法治愈，因此需要继续寻找其他治疗方案。骨髓环境中MM细胞的广泛分子和基因组表征影响骨髓瘤细胞的生长和存活，提供了许多新的药物靶点和途径。在多个水平的蛋白质catalysts的扰动已成为MM的一个重要目标。类似地，随着单克隆抗体产生和疫苗开发的改进沿着细胞表面和细胞靶点数量的鉴定，已经导致了各种策略的开发，包括正在临床前和早期临床研究中研究的抗体和抗体-药物缀合物。我们建议，最终，将需要分子信息的多药物联合治疗来消除MM细胞克隆，以实现长期疾病控制。
Multiple myeloma (MM) is the second most common hematologic malignancy affecting terminally differentiated plasma cells. Although high-dose chemotherapy and autologous stem cell transplantation improved survival in younger patients, the natural history of MM has been changed with the availability of five new agents approved in last 10 years (thalidomide, bortezomib, lenalidomide, liposomal doxorubicin and carfilzomib). Despite this significant improvement in overall outcome, MM remains incurable in majority of patients prompting continued search for additional therapeutic options. Extensive molecular and genomic characterization of MM cells in its bone marrow milieu, which affects myeloma cell growth and survival, has provided number of novel drugable targets and pathways. Perturbation of protein catabolism at multiple levels has become an important target in MM. Similarly with improvements in monoclonal antibody generation and vaccine development along with identification of number of cell surface and cellular targets have led to development of various strategies including antibodies and antibody-drug conjugates which are under investigation both preclinically as well as in early clinical studies. We propose that eventually, molecularly-informed multi-agent combination therapies will be required to eliminate the MM cell clone for a long-term disease control.