多发性骨髓瘤的信号通路及其靶向治疗的研究进展

Research progress on signal pathways and targeted therapy of multiple myeloma

多发性骨髓瘤(multiple myeloma,MM)是一种常见的血液系统恶性肿瘤。目前,广泛认可的治疗方法包括蛋白酶体抑制剂、化疗、免疫调节剂、干细胞移植和单克隆抗体治疗。随着新的治疗选择以及创新诊断方法的应用,患者生存期显著延长,但由于复发、耐药性的存在,它仍然是一种不可治愈的疾病。MM细胞的生长和存活依赖于肿瘤微环境中的细胞和非细胞成分,如骨髓基质细胞、内皮细胞和细胞因子,这种相互作用的累积效应使MM细胞内多种信号转导途径异常激活,最终导致MM细胞的增殖、存活、迁移和耐药性发生改变。探究这些信号通路与MM发病以及疾病进展之间的关系,寻找针对信号通路的新治疗靶点,是阐明MM发病机制以及治疗MM患者最有效的方法之一。目前针对信号通路的靶向治疗药物部分已在临床应用中取得成效,但部分仍处于基础研究。未来,针对信号通路的靶向治疗将是MM患者治愈的关键。本文就近年来MM的信号通路及其靶向治疗的研究进展进行综述。

Multiple myeloma(MM)is one kind of hematological system malignancies commonly.Currently,widely recognized treatment methods include proteasome inhibitors,chemotherapy,immune modulation,stem cell transplantation,and monoclonal antibody therapy.With the application of new treatment options and innovative diagnostic methods,the survival time of patients was significantly prolonged,but it is still an incurable disease,due to the relapse and drug resistance.MM cells are dependent on both cellular and non-cellular components of the tumor microenvironment such as bone marrow stromal cells,endothelial cells,and cytokines.The cumulative effect of such interactions is the aberrant activation of numerous signal transduction pathways within the MM cells leading to the proliferation,survival,migration and drug resistance of MM cells.Exploring the relationship between these signaling pathways and the pathogenesis and disease progression of MM,and finding new therapeutic targets for signaling pathways is the key to elucidating the pathogenesis of MM,and it is also one of the most effective methods for treating MM patients.At present,some targeted therapy drugs that targeting signal pathways have achieved success in clinical applications,but some are still in researching.In the future,targeted therapy for signaling pathways will be the key to the cure of MM patients.This article reviews the research progress of MM signaling pathway and its targeted therapy in recent years.