Emerging Therapeutic Strategies to Overcome Drug Resistance in Multiple Myeloma.
Emerging Therapeutic Strategies to Overcome Drug Resistance in Multiple Myeloma.
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DOI：
10.3390/cancers13071686
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发表时间：
2021-04-02
期刊：
影响因子：
5.2
通讯作者：
Sherbenou DW
中科院分区：
文献类型：
--
作者：
Davis LN;Sherbenou DW
多发性骨髓瘤是一种致命的血癌，但幸运的是，药物的开发大大延长了患者的寿命，在诊断出最佳治疗后，平均寿命超过十年。因此，患有多发性骨髓瘤的患者群体大幅增长。在整个过程中，患者反复复发，需要新的治疗方法。目前，用于治疗的关键药物类别是免疫调节药物、蛋白酶体抑制剂和单克隆抗体。这篇综述的目的是总结对这些药物的耐药性问题的理解，这是最终导致患者死亡的原因。此外，我们将重点关注在临床试验中有希望的新药如何克服耐药性。多发性骨髓瘤是一种恶性浆细胞肿瘤，仍然无法治愈，当患者获得多药耐药性时最终是致命的。因此，推进我们对多次复发患者耐药性背后机制的理解，对于开发更好的策略来延长他们的寿命至关重要。在这里，我们回顾了对三种主要的多发性骨髓瘤治疗药物的耐药性：免疫调节药物、蛋白酶体抑制剂和单克隆抗体。我们考虑多发性骨髓瘤复杂的异质生物学如何影响耐药性的获得，并反映需要额外研究以改善我们的治疗方法的知识差距。幸运的是，许多药物目前正在临床前和临床试验中进行评估，这些药物有可能克服或延迟耐药性，包括下一代免疫调节药物和蛋白酶体抑制剂，新型小分子药物，嵌合抗原受体T细胞，抗体-药物缀合物和双特异性抗体。对于每一类，我们讨论了这些策略的潜力，以克服耐药性通过修饰剂在每一类或新的类没有交叉耐药性，目前可用的药物。
Multiple myeloma is a deadly blood cancer, but fortunately drug development has substantially prolonged the lifespan of patients to average more than a decade after diagnosis with optimal therapy. As a result, the population of patients living with multiple myeloma has grown considerably. Through its course, patients suffer repeated relapses for which they require new lines of treatment. Currently, the key drug classes for treatment are immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies. The goal of this review is to summarize the understanding of the problem of resistance to these drugs, which is ultimately responsible for patient fatality. In addition, we will focus on how new agents that are promising in clinical trials overcome resistance. Multiple myeloma is a malignant plasma cell neoplasm that remains incurable and is ultimately fatal when patients acquire multi-drug resistance. Thus, advancing our understanding of the mechanisms behind drug resistance in multi-relapsed patients is critical for developing better strategies to extend their lifespan. Here, we review the understanding of resistance to the three key drug classes approved for multiple myeloma treatment: immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies. We consider how the complex, heterogenous biology of multiple myeloma may influence the acquisition of drug resistance and reflect on the gaps in knowledge where additional research is needed to improve our treatment approaches. Fortunately, many agents are currently being evaluated preclinically and in clinical trials that have the potential to overcome or delay drug resistance, including next-generation immunomodulatory drugs and proteasome inhibitors, novel small molecule drugs, chimeric antigen receptor T cells, antibody-drug conjugates, and bispecific antibodies. For each class, we discuss the potential of these strategies to overcome resistance through modifying agents within each class or new classes without cross-resistance to currently available drugs.
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影响因子：
11.4
作者：
Besse A;Stolze SC;Rasche L;Weinhold N;Morgan GJ;Kraus M;Bader J;Overkleeft HS;Besse L;Driessen C
通讯作者：
Driessen C
影响因子：
7.7
作者：
Acosta-Alvear D;Cho MY;Wild T;Buchholz TJ;Lerner AG;Simakova O;Hahn J;Korde N;Landgren O;Maric I;Choudhary C;Walter P;Weissman JS;Kampmann M
通讯作者：
Kampmann M
影响因子：
20.3
作者：
Catley, Laurence;Weisberg, Ellen;Anderson, Kenneth C.
通讯作者：
Anderson, Kenneth C.
影响因子：
11.4
作者：
Gandhi, Ujjawal H.;Cornell, Robert F.;Costa, Luciano J.
通讯作者：
Costa, Luciano J.
影响因子：
--
作者：
Baranowska K;Misund K;Starheim KK;Holien T;Johansson I;Darvekar S;Buene G;Waage A;Bjørkøy G;Sundan A
通讯作者：
Sundan A