Multiple myeloma (MM) is a highly heterogeneous malignant plasma cell disease. Proteasome inhibitors (PIs) are the first line of medicine for MM. Bortezomib, ixazomib, and carfilzomib are also widely used for MM. Marizomib, oprozomib, and KZR-616 are in clinical trials. However, the drug resistance of PIs in MM is still a problem. The mechanisms for PIs resistance to MM include ubiquitin-proteasome pathway, autophagy lysosome pathway, endoplasmic reticulum stress pathway, cell survival signal pathway, exosome-mediated resistance, and bone marrow microenvironment-mediated resistance.
多发性骨髓瘤(multiple myeloma，MM)是一种高度异质性恶性浆细胞疾病。蛋白酶体抑制剂(proteasome inhibitors，PIs)是治疗MM的一线药物，硼替佐米、伊莎佐米和卡非佐米也广泛应用于MM的治疗中，marizomib、奥泼佐米和KZR-616正在临床试验中。然而，PIs在MM中仍存在耐药问题。目前有关PIs对MM的耐药机制包括泛素-蛋白酶体通路、自噬溶酶体通路、内质网应激通路、细胞促存活信号通路，以及外泌体介导耐药和骨髓微坏境介导耐药。.
Keywords: drug resistance; multiple myeloma; proteasome inhibitor.