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小分子作为化疗药物克服多发性骨髓瘤耐药性的研究策略。

Research strategies of small molecules as chemotherapeutics to overcome multiple myeloma resistance.

机构信息

National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, Jiangsu, 210023, China.

National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, Jiangsu, 210023, China.

出版信息

Eur J Med Chem. 2024 May 5;271:116435. doi: 10.1016/j.ejmech.2024.116435. Epub 2024 Apr 20.

Abstract

Multiple myeloma (MM), a cancer of plasma cells, is the second most common hematological malignancy which is characterized by aberrant plasma cells infiltration in the bone marrow and complex heterogeneous cytogenetic abnormalities. Over the past two decades, novel treatment strategies such as proteasome inhibitors, immunomodulators, and monoclonal antibodies have significantly improved the relative survival rate of MM patients. However, the development of drug resistance results in the majority of MM patients suffering from relapse, limited treatment options and uncontrolled disease progression after relapse. There are urgent needs to develop and explore novel MM treatment strategies to overcome drug resistance and improve efficacy. Here, we review the recent small molecule therapeutic strategies for MM, and introduce potential new targets and corresponding modulators in detail. In addition, this paper also summarizes the progress of multi-target inhibitor therapy and protein degradation technology in the treatment of MM.

摘要

多发性骨髓瘤(MM)是一种浆细胞恶性肿瘤,其特征为骨髓中异常浆细胞浸润和复杂的细胞遗传学异常。在过去的二十年中,蛋白酶体抑制剂、免疫调节剂和单克隆抗体等新型治疗策略显著提高了 MM 患者的相对生存率。然而,耐药性的发展导致大多数 MM 患者复发,复发后治疗选择有限且疾病无法得到控制。因此,迫切需要开发和探索新的 MM 治疗策略以克服耐药性并提高疗效。在这里,我们综述了 MM 的最新小分子治疗策略,并详细介绍了潜在的新靶点和相应的调节剂。此外,本文还总结了多靶点抑制剂治疗和蛋白降解技术在 MM 治疗中的进展。

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