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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           Δ



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          卢传洋    1, 2* ,陈秋妮 ,史玉叶 ,邓 媛 ,纪婷婷 ,刘正媛 ,王春玲 ,于 亮 (1.南京医科大学附属淮
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          安第一医院血液科,江苏 淮安 223300;2.南京医科大学血液学重点实验室,南京 210029)
          中图分类号  R979.1;R733.4      文献标志码  A      文章编号  1001-0408(2026)05-0682-07
          DOI  10.6039/j.issn.1001-0408.2026.05.23
          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。
          关键词  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

          Advances in the JAK2/STAT3 signaling pathway and its inhibitors in diffuse large B cell lymphoma

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          LU Chuanyang ,CHEN Qiuni ,SHI Yuye ,DENG Yuan ,JI Tingting ,LIU Zhengyuan ,WANG
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          Chunling ,YU Liang (1.  Dept.  of  Hematology,  the  Affiliated  Huaian  No. 1  People's  Hospital  of  Nanjing
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          Medical  University,  Jiangsu  Huai’an  223300,  China;2.  Key  Laboratory  of  Hematology,  Nanjing  Medical
          University, Nanjing 210029, China)
          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.
          KEYWORDS     Janus  kinase;  signal  transducer  and  activator  of  transcription;  diffuse  large  B-cell  lymphoma;  ruxolitinib;
                                                              proteolysis targeting chimeras

              Δ 基金项目 淮 安 市 科 技 计 划 项 目 自 然 科 学 研 究 项 目(No.
          HAB2024002);淮安市自身免疫性疾病重点实验室计划项目(No.
                                                                  恶性淋巴瘤是一组起源于淋巴结和淋巴组织的具
          HAP202302);淮安市第一人民医院创新团队项目(No.YCT202306)
             *第一作者 硕士研究生。研究方向:淋巴瘤靶向治疗。E-mail:                 有异质性的血液系统肿瘤,根据其组织病理学特征主要
          luchuanyangdyx@163.com
                                                              分为霍奇金淋巴瘤(Hodgkin lymphoma,HL)和非霍奇
              # 通信作者 主任医师,博士生导师。研究方向:淋巴瘤靶向治疗。
          E-mail:yuliangha@163.com                            金淋巴瘤(non-Hodgkin lymphoma,NHL)两大类。弥漫


          · 682 ·    China Pharmacy  2026 Vol. 37  No. 5                               中国药房  2026年第37卷第5期
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