Chng Wee Joo, Lau Lee Gong, Yusof Noorainun, Mow Benjamin M F
Department of Hematology-Oncology, National University Hospital, 119074 Singapore.
Cancer Control. 2005 Apr;12(2):91-104. doi: 10.1177/107327480501200204.
Multiple myeloma (MM) is an incurable malignancy. Recent insights into its biology has allowed the use of novel therapies targeting not only the deregulated intracellular signaling in MM cells but also its interaction with the bone marrow microenvironment that confers drug resistance, growth, and survival advantage to the malignant cells.
We review and summarize the recent advances in our knowledge of myeloma biology as well as the mechanism of action and clinical efficacy for novel therapeutic agents in clinical trials.
Several novel therapeutic agents are currently in clinical trials. Thalidomide is already established for both initial and salvage treatment. Bortezomib is being tested alone and in combination with conventional chemotherapy in various settings. Other agents are less effective in producing response but have been able to stabilize disease in patients with relapsed and/or refractory disease, such as arsenic trioxide, farnesyltransferase inhibitors, 2-methoxyestradiol, and vascular endothelial growth factor receptor inhibitors. Insights into drug resistance mechanism have also led to the development of novel agents that sensitize myeloma cells to chemotherapy (Bcl-2 antisense). Gene expression studies have in many instances identified pathways other than the intended target of the drug and have provided insights into the therapeutic mechanisms.
In the future, patients with MM will have more therapeutic options available than ever before. The challenge will be to identify patient subgroups that will benefit most from the different therapies and then determine how these biologically based therapies could be combined and incorporated into the overall management of patients.
多发性骨髓瘤（MM）是一种无法治愈的恶性肿瘤。最近对其生物学特性的深入了解使得新型疗法得以应用，这些疗法不仅针对MM细胞中失调的细胞内信号传导，还针对其与骨髓微环境的相互作用，骨髓微环境赋予恶性细胞耐药性、生长和生存优势。
我们回顾并总结了骨髓瘤生物学知识的最新进展以及新型治疗药物在临床试验中的作用机制和临床疗效。
目前有几种新型治疗药物正在进行临床试验。沙利度胺已被确立用于初始治疗和挽救治疗。硼替佐米正在单独以及在各种联合方案中与传统化疗联合进行测试。其他药物在产生反应方面效果较差，但能够使复发和/或难治性疾病患者的病情稳定，如三氧化二砷、法尼基转移酶抑制剂、2-甲氧基雌二醇和血管内皮生长因子受体抑制剂。对耐药机制的深入了解还导致了使骨髓瘤细胞对化疗敏感的新型药物（Bcl-2反义核酸）的开发。基因表达研究在许多情况下确定了药物预期靶点以外的途径，并提供了对治疗机制的深入了解。
未来，MM患者将比以往有更多的治疗选择。挑战将是确定最能从不同疗法中获益的患者亚组，然后确定如何将这些基于生物学的疗法联合起来并纳入患者的整体管理中。
