Penn State Hershey Cancer Institute, Penn State Milton S. Hershey Medical Center, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Adv Exp Med Biol. 2013;779:197-221. doi: 10.1007/978-1-4614-6176-0_9.
Multiple myeloma (MM) is a plasma cell malignancy and the second most common hematologic cancer. MM is characterized by the accumulation of malignant plasma cells within the bone marrow, and presents clinically with a broad range of symptoms, including hypercalcemia, renal insufficiency, anemia, and lytic bone lesions. MM is a heterogeneous disease associated with genomic instability, where patients may express multiple genetic abnormalities that affect several oncogenic pathways. Commonly detected genetic aberrations are translocations involving immunoglobulin heavy chain (IgH) switch regions (chromosome 14q32) and oncogenes such as c-maf [t(14:16)], cyclin D1 [t(11:14)], and FGFR3/MMSET [t(4:14)]. Advances in the basic understanding of MM and the development of novel agents, such as the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide and the proteasome inhibitor bortezomib, have increased therapeutic response rates and prolonged patient survival. Despite these advances MM remains incurable in the majority of patients, and it is therefore critical to identify additional therapeutic strategies and targets for its treatment. In this chapter, we review the underlying genetic components of MM and discuss the results of recent clinical trials that demonstrate the effectiveness of targeted agents in the management of MM. In addition, we discuss experimental therapies that are currently in clinical development along with their molecular rationale in the treatment of MM.
多发性骨髓瘤（MM）是一种浆细胞恶性肿瘤，也是第二常见的血液系统恶性肿瘤。MM 的特征是恶性浆细胞在骨髓内积聚，并表现出广泛的临床症状，包括高钙血症、肾功能不全、贫血和溶骨性骨病变。MM 是一种与基因组不稳定性相关的异质性疾病，患者可能表达多种影响多个致癌途径的遗传异常。常见的遗传异常包括涉及免疫球蛋白重链（IgH）开关区（染色体 14q32）和癌基因的易位，如 c-maf[t(14:16)]、cyclin D1[t(11:14)]和 FGFR3/MMSET[t(4:14)]。对 MM 的基础理解的进展以及新型药物的开发，如免疫调节药物（IMiDs）沙利度胺和来那度胺以及蛋白酶体抑制剂硼替佐米，提高了治疗反应率并延长了患者的生存期。尽管取得了这些进展，但 MM 在大多数患者中仍然无法治愈，因此识别额外的治疗策略和靶点对于其治疗至关重要。在本章中，我们回顾了 MM 的潜在遗传成分，并讨论了最近临床试验的结果，这些试验表明靶向药物在 MM 治疗中的有效性。此外，我们还讨论了目前正在临床开发中的实验性疗法及其在 MM 治疗中的分子原理。
