Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg.
College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.
Biochem Pharmacol. 2021 Jun;188:114526. doi: 10.1016/j.bcp.2021.114526. Epub 2021 Mar 17.
Multiple myeloma (MM) is a biologically complex hematological disorder defined by the clonal proliferation of malignant plasma cells producing excessive monoclonal immunoglobulin that interacts with components of the bone marrow microenvironment, resulting in the major clinical features of MM. Despite the development of numerous protocols to treat MM patients, this cancer remains currently incurable; due in part to the emergence of resistant clones, highlighting the unmet need for innovative therapeutic approaches. Accumulating evidence suggests that the survival of MM molecular subgroups depends on the expression profiles of specific subsets of anti-apoptotic B-cell lymphoma (BCL)-2 family members. This review summarizes the mechanisms underlying the anti-myeloma activities of the potent BCL-2 family protein inhibitors, individually or in combination with conventional therapeutic options, and provides an overview of the strong rationale to clinically investigate such interventions for MM therapy.
多发性骨髓瘤（MM）是一种生物学上复杂的血液系统疾病，其特征是恶性浆细胞的克隆性增殖，产生过多的单克隆免疫球蛋白，与骨髓微环境的成分相互作用，导致 MM 的主要临床特征。尽管已经制定了许多方案来治疗 MM 患者，但这种癌症目前仍然无法治愈；部分原因是耐药克隆的出现，这突显了对创新治疗方法的需求未得到满足。越来越多的证据表明，MM 分子亚群的存活取决于特定亚群抗凋亡 B 细胞淋巴瘤（BCL）-2 家族成员的表达谱。这篇综述总结了强效 BCL-2 家族蛋白抑制剂的抗骨髓瘤活性的作用机制，这些抑制剂单独或与传统治疗方法联合使用，并概述了将这些干预措施用于 MM 治疗的临床研究的强有力理由。
