Institute of Cancer Research and Royal Marsden Hospital, London, United Kingdom.
Hematology Am Soc Hematol Educ Program. 2012;2012:342-9. doi: 10.1182/asheducation-2012.1.342.
Recent advances in multiple myeloma (MM) therapy have led to significantly longer median survival rates and some patients being cured. At the same time, our understanding of MM biology and the molecular mechanisms driving the disease is constantly improving. Next-generation sequencing technologies now allow insights into the genetic aberrations in MM at a genome-wide scale and across different developmental stages in the course of an individual tumor. This improved knowledge about MM biology needs to be rapidly translated and transformed into diagnostic and therapeutic applications to finally achieve cure in a larger proportion of patients. As a part of these translational efforts, novel drugs that inhibit oncogenic proteins overexpressed in defined molecular subgroups of the disease, such as FGFR3 and MMSET in t(4;14) MM, are currently being developed. The potential of targeted next-generation diagnostic tests to rapidly identify clinically relevant molecular subgroups is being evaluated. The technical tools to detect and define tumor subclones may potentially become clinically relevant because intraclonal tumor heterogeneity has become apparent in many cancers. The emergence of different MM subclones under the selective pressure of treatment is important in MM, especially in the context of maintenance therapy and treatment for asymptomatic stages of the disease. Finally, novel diagnostic and therapeutic achievements have to be implemented into innovative clinical trial strategies with smaller trials for molecularly defined high-risk patients and large trials with a long follow-up for the patients most profiting from the current treatment protocols. These combined approaches will hopefully transform the current one-for-all care into a more tailored, individual therapeutic strategy for MM patients.
近年来，多发性骨髓瘤（MM）治疗取得了显著进展，中位生存率明显延长，部分患者得到治愈。与此同时，我们对 MM 生物学和驱动疾病的分子机制的理解也在不断提高。下一代测序技术现在可以在全基因组范围内和个体肿瘤发展的不同阶段深入了解 MM 的遗传异常。关于 MM 生物学的这些新知识需要迅速转化为诊断和治疗应用，最终使更大比例的患者得到治愈。作为这些转化努力的一部分，目前正在开发针对疾病特定分子亚群中过表达的致癌蛋白的新型药物，如 FGFR3 和 MMSET 在 t(4;14) MM 中。正在评估靶向下一代诊断测试快速识别临床相关分子亚群的潜力。检测和定义肿瘤亚克隆的技术工具可能具有临床相关性，因为在许多癌症中已经明显存在克隆内肿瘤异质性。在治疗的选择压力下出现不同的 MM 亚克隆在 MM 中很重要，特别是在维持治疗和无症状疾病阶段的治疗背景下。最后，新的诊断和治疗成果必须纳入创新的临床试验策略中，对于分子定义的高危患者进行较小规模的试验，对于从当前治疗方案中获益最大的患者进行长期随访的大规模试验。这些综合方法有望将当前的一刀切治疗模式转变为更适合 MM 患者的个体化治疗策略。
