骨髓瘤耐药相关机制及联合HDACi治疗多发性骨髓瘤

摘要

Drug resistance of multiple myeloma(MM) has become more and more common,and greatly decreased the survival rate of these patients.The occurence of drug-resistance involves in many factors such as bone marrow microenveronment,tumor cell self-metabolism,cytokines,specific targets and so on.In this review,the potential mechanisms of resistance to glucocorticoid/proteasome inhibitor/immunomodulatory druges are briefly expounded in the aspect of tumor cell self-metabolism,including the changes of heat slock protein expression,mRNA expression,related cytokine levels and down-regulation of thalidomid-effecting site CRBN expression.In this review,the researches on the effect of histone deacetylase inhibitors (HDACi) combined with glucocorticoid,proteasome inhibitors,immunomodulatory drugs and monoclonal antibodies on multiple myeloma,specially,drug-resistant multiple myeloma are also summarized.%由于各类非细胞毒类药物应用于多发性骨髓瘤逐渐增多,相继产生的耐药已成为多发性骨髓瘤患者进一步延长生存的巨大障碍.耐药的产生涉及到骨髓微环境、瘤细胞本身代谢、细胞因子及特异性靶点的下调等诸多方面因素.本文从骨髓瘤细胞本身改变,其中包括热休克蛋白表达的改变、miRNA表达水平的改变、代谢改变、相关细胞因子水平的变化及沙利度胺作用位点CRBN表达下调,进而从多方面阐述了骨髓瘤耐药的机制,并且系统地概括了小分子表观遗传学药物组蛋白去乙酰化抑制剂联合激素、蛋白酶体抑制剂、免疫调节剂及单抗等在治疗多发性骨髓瘤尤其是耐药骨髓瘤方面的诸多问题.