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JAK2/STAT3信号通路及其抑制剂在弥漫大B细胞淋巴瘤中的研究进展
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| 篇名： | JAK2/STAT3信号通路及其抑制剂在弥漫大B细胞淋巴瘤中的研究进展 |
| TITLE： | Advances in the JAK2/STAT3 signaling pathway and its inhibitors in diffuse large B cell lymphoma |
| 摘要： | Janus激酶/信号转导和转录激活因子（JAK/STAT）信号通路的异常激活参与了弥漫大B细胞淋巴瘤（DLBCL）的发病。近些年来，靶向JAK2和STAT3的抑制剂在DLBCL的治疗研究中展现出潜力。本文综述了JAK2抑制剂（如芦可替尼）和STAT3抑制剂（包括直接靶向STAT3的小分子抑制剂、反义寡核苷酸、蛋白降解靶向嵌合体等）在临床前研究及临床试验中的疗效与安全性。结果表明，JAK2和STAT3抑制剂在部分DLBCL患者中表现出抗肿瘤活性和良好的耐受性；同时，新型药物递送系统的开发显著提升了化合物的稳定性、生物利用度与靶向能力；此外，JAK2和STAT3抑制剂与其他治疗方案（如与B细胞受体信号通路抑制剂、免疫调节剂或其他靶向药物等的联合）联合可能表现出协同效应。但现有临床应用仍处于早期阶段，未来的研究应聚焦于基于DLBCL遗传分型的精准治疗策略，并进一步优化抑制剂的递送系统及联合用药方案，以提升临床疗效。 |
| ABSTRACT： | Abnormal activation of the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway is involved in the pathogenesis of diffuse large B-cell lymphoma （DLBCL）. In recent years， inhibitors targeting JAK2 and STAT3 have emerged as promising therapeutic candidates in DLBCL. This review summarizes the efficacy and safety profiles of JAK2 inhibitors （e.g.， ruxolitinib） and STAT3 inhibitors （direct small-molecule inhibitors， the antisense oligonucleotide， and proteolysis targeting chimeras， etc.） in preclinical models and clinical trials. Accumulating evidence indicates that JAK2 and STAT3 inhibitors exhibit antitumor activity and are generally well tolerated in a subset of DLBCL patients. Meanwhile， the development of novel drug delivery systems has significantly enhanced the stability， bioavailability， and targeting ability of the compounds. Furthermore， JAK2 and STAT3 inhibitors may exhibit synergistic effects when combined with other therapy strategies （such as combinations with B-cell receptor signaling pathway inhibitors， immunomodulators， or other targeted drugs）. However， current clinical applications are still in their early stages. Future research should concentrate on precision treatment strategies based on the genetic subtyping of DLBCL， and further refine the delivery systems for inhibitors as well as combination drug regimens to improve clinical outcomes. |
| 期刊： | 2026年第37卷第05期 |
| 作者： | 卢传洋；陈秋妮；史玉叶；邓媛；纪婷婷；刘正媛；王春玲；于亮 |
| AUTHORS： | LU Chuanyang，CHEN Qiuni，SHI Yuye，DENG Yuan，JI Tingting，LIU Zhengyuan，WANG Chunling，YU Liang |
| 关键字： | Janus激酶；信号转导和转录激活因子；弥漫大B细胞淋巴瘤；芦可替尼；蛋白降解靶向嵌合体 |
| KEYWORDS： | Janus kinase； signal transducer and activator of transcription； diffuse large B-cell lymphoma； ruxolitinib； |
| 阅读数： | 7 次 |
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