New effective strategies are required that specifically address the challenges of multiple myeloma (MM) treatment, namely, disease recurrence, immunosuppression, and treatment-related toxicities. Recent preclinical and clinical findings suggest that the IMiDs® immunomodulatory compound lenalidomide has a dual mechanism of action, involving both a direct tumoricidal activity and immunomodulation, which may result in rapid and sustained control of MM, respectively. The tumoricidal effect of lenalidomide occurs through several mechanisms, including disruption of stromal support, induction of tumor suppressor genes, and activation of caspases. The immunomodulatory effects of lenalidomide, including T-cell and natural killer (NK)-cell activation, and increased expression of death effector molecules, lead to enhanced immune cell function and may explain the beneficial effects of this agent in the maintenance setting. Lenalidomide appears to be effective regardless of prior thalidomide treatment, which may reflect mechanistic differences - lenalidomide has greater immunomodulatory properties than thalidomide, whereas thalidomide has greater antiangiogenic activity. Recent studies also suggest that the concomitant use of dexamethasone may influence lenalidomide's direct and immunomodulatory effects. Lenalidomide in combination with dexamethasone synergistically inhibits proliferation and induces apoptosis; however, dexamethasone appears to antagonize the immune-enhancing effect of lenalidomide. A study has demonstrated that a regimen of lenalidomide in combination with an optimal dose and schedule of dexamethasone may increase survival by allowing synergistic antiproliferative effects, without affecting immunomodulatory activity. As preclinical and clinical research continue, additional insights into the dual mechanism of action of lenalidomide will help to further optimize the use of lenalidomide in MM.

中文翻译：

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来那度胺的作用方式：将试验台和临床发现联系起来。

需要新的有效策略来专门应对多发性骨髓瘤（MM）治疗的挑战，即疾病复发，免疫抑制和与治疗相关的毒性。最近的临床前和临床发现表明，免疫调节化合物来那度胺具有双重作用机制，涉及直接的杀肿瘤活性和免疫调节作用，分别可能导致对MM的快速和持续控制。来那度胺的杀肿瘤作用通过几种机制发生，包括基质支持的破坏，肿瘤抑制基因的诱导和胱天蛋白酶的激活。来那度胺的免疫调节作用，包括T细胞和自然杀伤（NK）细胞激活，以及死亡效应分子的增加表达，导致增强的免疫细胞功能，并可以解释这种药物在维持环境中的有益作用。来那度胺似乎是有效的，而不论先前的沙利度胺治疗如何，这可能反映出机理上的差异-来那度胺比沙利度胺具有更大的免疫调节特性，而沙利度胺具有更大的抗血管生成活性。最近的研究还表明，地塞米松的同时使用可能会影响来那度胺的直接和免疫调节作用。来那度胺与地塞米松联用可协同抑制增殖并诱导凋亡。然而，地塞米松似乎拮抗来那度胺的免疫增强作用。一项研究表明，来那度胺方案与地塞米松的最佳剂量和时间表相结合可通过产生协同抗增殖作用而增加存活率，而不会影响免疫调节活性。随着临床前和临床研究的继续，对来那度胺双重作用机制的更多见解将有助于进一步优化来那度胺在MM中的使用。