Choudhry Priya, Galligan Derek, Wiita Arun P
Department of Laboratory Medicine, University of California, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA; These authors contributed equally.
Department of Medicine, University of California, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA; These authors contributed equally.
Trends Cancer. 2018 Aug;4(8):567-582. doi: 10.1016/j.trecan.2018.05.005. Epub 2018 Jun 27.
For over a decade, the mainstay of multiple myeloma therapy has been small molecules that directly attack malignant plasma cell biology. However, potent immunotherapies have recently emerged, transforming the myeloma therapeutic landscape. Here we first review new promising strategies to target plasma cells through protein homeostasis and epigenetic modulators. We then discuss emerging immunotherapy strategies that are leading to dramatic results in patients. Finally, we focus on recent preclinical data suggesting that enforcing cell-surface antigen expression through small molecules may enhance immunotherapy efficacy and avoid resistance. We argue that these emerging observations point the way toward potential convergence between drug classes. With recent rapid progress we may finally be on the verge of the 'C' word: a cure for myeloma.
十多年来,多发性骨髓瘤治疗的主要手段一直是直接攻击恶性浆细胞生物学特性的小分子药物。然而,强效免疫疗法最近出现了,改变了骨髓瘤的治疗格局。在此,我们首先回顾通过蛋白质稳态和表观遗传调节剂靶向浆细胞的新的有前景的策略。然后,我们讨论在患者中取得显著疗效的新兴免疫治疗策略。最后,我们关注最近的临床前数据,这些数据表明通过小分子增强细胞表面抗原表达可能会提高免疫治疗效果并避免耐药性。我们认为,这些新出现的观察结果为不同药物类别之间的潜在融合指明了方向。随着最近的快速进展,我们最终可能即将迎来那个“C”字:治愈骨髓瘤。