Acquired resistance to immunomodulatory drugs (IMiDs) remains a significant unmet need in the treatment landscape of multiple myeloma (MM). CRBN pathway-dependent mechanisms are known to be vital contributors to IMiD resistance; however, they may account for only a small proportion. Recent research has unveiled additional mechanisms of acquired IMiD resistance that are independent of the CRBN pathway. In this review, we provide a comprehensive overview of the existing work on IMiD resistance in MM, focusing specifically on the emerging evidence of CRBN pathway-independent mechanisms. Finally, we discuss the plausible actionable strategies and outlook for IMiD-based therapies moving forward.

中文翻译：

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多发性骨髓瘤对免疫调节药物的耐药性：cereblon 途径及其他。


对免疫调节药物 （IMiD） 的获得性耐药仍然是多发性骨髓瘤 （MM） 治疗领域未满足的重大需求。已知 CRBN 通路依赖性机制是 IMiD 耐药的重要因素;但是，它们可能只占很小的一部分。最近的研究揭示了独立于 CRBN 通路的获得性 IMiD 耐药的其他机制。在这篇综述中，我们全面概述了 MM 中 IMiD 耐药的现有工作，特别关注 CRBN 通路非依赖性机制的新证据。最后，我们讨论了基于 IMiD 的疗法向前发展的合理可行策略和前景。