Hu Shuoyang, Xu Jirun, Cui Weiyan, Jin Haoran, Wang Xiaoyu, Maimaitiyiming Yasen
Department of Immunology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi 830011, China.
Xinjiang Key Laboratory of Molecular Biology for Endemic Diseases, Xinjiang Medical University, Urumqi 830011, China.
Biomolecules. 2025 May 12;15(5):702. doi: 10.3390/biom15050702.
Multiple myeloma (MM) remains an incurable hematologic malignancy due to the inevitable development of drug resistance, particularly in relapsed or refractory cases. Post-translational modifications (PTMs), including phosphorylation, ubiquitination, acetylation, and glycosylation, play pivotal roles in regulating protein function, stability, and interactions, thereby influencing MM pathogenesis and therapeutic resistance. This review comprehensively explores the mechanisms by which dysregulated PTMs contribute to drug resistance in MM, focusing on their impact on key signaling pathways, metabolic reprogramming, and the tumor microenvironment. We highlight how PTMs modulate drug uptake, alter drug targets, and regulate cell survival signals, ultimately promoting resistance to PIs, IMiDs, and other therapeutic agents. Furthermore, we discuss emerging therapeutic strategies targeting PTM-related pathways, which offer promising avenues for overcoming resistance to treatment. By integrating preclinical and clinical insights, this review underscores the potential of PTM-targeted therapies to enhance treatment efficacy and improve patient outcomes in MM.
由于不可避免地会产生耐药性，尤其是在复发或难治性病例中，多发性骨髓瘤（MM）仍然是一种无法治愈的血液系统恶性肿瘤。翻译后修饰（PTM），包括磷酸化、泛素化、乙酰化和糖基化，在调节蛋白质功能、稳定性和相互作用方面起着关键作用，从而影响MM的发病机制和治疗耐药性。本综述全面探讨了失调的PTM导致MM耐药的机制，重点关注它们对关键信号通路、代谢重编程和肿瘤微环境的影响。我们强调PTM如何调节药物摄取、改变药物靶点并调节细胞存活信号，最终促进对蛋白酶体抑制剂（PI）、免疫调节药物（IMiD）和其他治疗药物的耐药性。此外，我们讨论了针对PTM相关途径的新兴治疗策略，这些策略为克服治疗耐药性提供了有希望的途径。通过整合临床前和临床见解，本综述强调了PTM靶向治疗在提高MM治疗效果和改善患者预后方面的潜力。
