Davis Lorraine N, Sherbenou Daniel W
Division of Hematology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Department of Blood Disorders and Cell Therapies, University of Colorado Comprehensive Cancer Center, Aurora, CO 80045, USA.
Cancers (Basel). 2021 Apr 2;13(7):1686. doi: 10.3390/cancers13071686.
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.
多发性骨髓瘤是一种恶性浆细胞瘤，目前仍无法治愈，当患者产生多药耐药性时最终会导致死亡。因此，深入了解多次复发患者耐药背后的机制对于制定延长其生存期的更好策略至关重要。在此，我们综述了对批准用于多发性骨髓瘤治疗的三类关键药物耐药性的理解：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、异质性的生物学特性如何影响耐药性的产生，并反思知识上的差距，即需要进行更多研究以改进我们的治疗方法。幸运的是，目前许多药物正在临床前和临床试验中进行评估，它们有可能克服或延缓耐药性，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、抗体药物偶联物和双特异性抗体。对于每一类药物，我们讨论这些策略通过修饰每一类药物中的药物或新的无交叉耐药性的药物类别来克服耐药性的潜力。
