多发性骨髓瘤（MM）是一种异质性浆细胞肿瘤，生存期为数月至十年以上。尽管开发了各种新药，MM仍然无法治愈并且反复复发。硼替佐米是多发性骨髓瘤治疗史上的一个里程碑事件，它极大地改善了多发性骨髓瘤患者的预后。虽然以硼替佐米为代表的蛋白酶体抑制剂（PI）极大地延长了MM的生存期，但不幸的是，几乎所有MM都会产生硼替佐米耐药，导致复发，生存期缩短。据报道，肿瘤微环境和骨髓瘤细胞都会导致硼替佐米耐药。人们尝试了多种治疗方法来克服硼替佐米耐药性，但不幸的是，尚未取得突破。据信，关键的耐药机制尚未被发现。更深入地了解硼替佐米耐药机制和克服策略有助于识别关键耐药机制并进一步改善 MM 的预后。© 2024。作者获得 Springer Science Business Media, LLC 的独家许可，该公司是施普林格自然。

Multiple myeloma (MM) is a heterogeneous plasma cell tumor with a survival period of several months to over ten years. Despite the development of various new drugs, MM is still incurable and recurs repeatedly. Bortezomib, a landmark event in the history of MM treatment, has dramatically improved the prognosis of patients with MM. Although proteasome inhibitors (PIs) represented by bortezomib, have greatly prolonged MM survival, unfortunately, almost all MM will develop bortezomib resistance, leading to relapse with a shorter survival. It has been reported that both the tumor microenvironment and myeloma cells drive bortezomib resistance. Multiple treatment methods have been attempted to overcome bortezomib resistance, but unfortunately, there has been no breakthrough. It is believed that the key resistance mechanism has not yet been discovered. A deeper understanding of the mechanism of bortezomib resistance and strategies to overcome it can help identify key resistance mechanisms and further improve the prognosis of MM.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.