Srikanth Muralikrishnan, Davies Faith E, Morgan Gareth J
The Royal Marsden Hospital, Department of Haemato-Oncology, Downs Road, Sutton, Surrey SM2 5PT, UK.
Expert Opin Investig Drugs. 2008 Jan;17(1):1-12. doi: 10.1517/13543784.17.1.1.
Multiple myeloma is the second most common haematological malignancy. It is becoming increasingly manageable with conventional and high-dose chemotherapy but there remains a critical need to develop both new drugs and combinations to improve long-term outcomes. Novel biological therapies that specifically target myeloma cells and/or their microenvironmental interactions are being developed that are highly effective, both as single agents and as combinations. Chief among these new agents are the proteasome inhibitor, bortezomib, and the immunomodulatory agents, thalidomide and lenalidomide. These drugs show improved single agent activity that is enhanced in combination. However, many drugs that are being developed in this setting may only have limited single agent activity, but combination use with these and other agents represents a very exciting way of targeting important pathogenic pathways crucial in myeloma development. This represents a challenge for both drug development and clinical trial evaluation, which has the potential to revolutionise the clinical management of myeloma and a paradigm for drug development in other diseases.
多发性骨髓瘤是第二常见的血液系统恶性肿瘤。通过传统化疗和大剂量化疗，其病情越来越易于控制，但仍迫切需要研发新药物及联合用药方案以改善长期治疗效果。目前正在研发特异性靶向骨髓瘤细胞和/或其微环境相互作用的新型生物疗法，这些疗法无论是作为单一药物还是联合用药都具有高效性。这些新药物中，蛋白酶体抑制剂硼替佐米、免疫调节剂沙利度胺和来那度胺最为突出。这些药物单药活性有所提高，联合用药时活性更强。然而，在此背景下研发的许多药物单药活性可能有限，但与这些药物及其他药物联合使用是一种非常有前景的方式，可针对骨髓瘤发展过程中至关重要的重要致病途径。这对药物研发和临床试验评估而言都是一项挑战，有可能彻底改变骨髓瘤的临床管理方式，并为其他疾病的药物研发树立典范。
