Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
Leuk Lymphoma. 2013 Feb;54(2):229-41. doi: 10.3109/10428194.2012.706287. Epub 2012 Sep 17.
The prognosis of patients with multiple myeloma (MM) has radically changed over the past two decades mostly due to the introduction of novel pharmacologic treatments such as thalidomide, bortezomib and lenalidomide. These drugs were the first new anti-myeloma agents since the 1950s, and represented a landmark step in the race for the cure of MM and the paradigm of effectiveness of bench-to-bedside research. Compared to a median overall survival of 2-3 years in the mid-1950s, patients with MM have nowadays an expected median survival of 7-8 years. Novel agents have not only extended the life expectancy of patients with MM, but also shed light on the necessity of further understanding the biology of MM in order to design more effective, less toxic therapies. Basic research has provided a critical mass of information about the molecular and cellular biology of MM, particularly the pivotal pathogenetic role of the bone marrow niche. Several novel drugs, designed to specifically target MM in the context of its microenvironment, are currently in clinical trials and hold great promise for improving the MM treatment armamentarium and overcoming resistance. In this article we review the biological basis of effectiveness of anti-myeloma agents with an emphasis on experimental drugs.
过去二十年中，由于新型药物的出现，多发性骨髓瘤（MM）患者的预后发生了巨大变化。这些药物是自 20 世纪 50 年代以来的首批新型抗骨髓瘤药物，代表着治愈 MM 的竞赛中的一个里程碑，也是从基础研究到临床实践的典范。与 20 世纪 50 年代中期患者的中位总生存期 2-3 年相比，目前 MM 患者的中位生存期为 7-8 年。新型药物不仅延长了 MM 患者的预期寿命，而且也使我们进一步认识到 MM 生物学的必要性，以便设计更有效、毒性更小的治疗方法。基础研究为 MM 的分子和细胞生物学提供了大量信息，特别是骨髓微环境中发病机制的关键作用。目前，几种旨在针对 MM 及其微环境的特定药物正在临床试验中，它们为改善 MM 的治疗手段和克服耐药性提供了很大的希望。本文综述了抗骨髓瘤药物疗效的生物学基础，重点介绍了实验药物。
