曲妥珠单抗耐药机制研究进展-国际临床研究杂志-CSCIED科技核心评价数据库-手机版

曲妥珠单抗耐药机制研究进展

Advances on Resistance Mechanisms of Trastuzumab

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DOI	10.12208/j.ijcr.20220048
刊名	国际临床研究杂志 International Journal of Clinical Research
年，卷(期)	2022, 6(2)
作者	邢一舒,王赛琪,吕慧芳,聂彩云,王建正,赵慧晨,陈小兵*,
作者单位	郑州大学附属肿瘤医院，河南省肿瘤医院消化内科河南郑州 ;
摘要	曲妥珠单抗是首个靶向人类表皮生长因子受体-2（Human Epidermal Growth Factor Receptor 2，HER2）的人源化单克隆抗体药物，极大地改善了HER2阳性乳腺癌与胃癌患者的治疗效果及预后，成为HER2阳性晚期乳腺癌与胃癌一线治疗策略。然而，多数患者在使用曲妥珠单抗治疗一年后发生继发耐药，导致疾病进展。研究表明，HER2蛋白结构改变、其他人类表皮生长因子受体（Human Epidermal Growth Factor Receptor，HER）家族受体及其配体信号通路激活、下游磷脂酰肌醇-3激酶（phosphoinositide-3-kinase，PI3K）信号通路改变、上皮间质转化（epithelial-mesenchymal transition，EMT）发生以及抗体依赖的细胞介导的细胞毒作用 (antibody-dependent cell-mediated cytotoxicity，ADCC)等多种机制参与了曲妥珠单抗耐药，本文就曲妥珠单抗耐药机制进行综述，为曲妥珠单抗的治疗提供预测生物标志物、克服耐药的方法，进行更加有效的靶向用药或者联合治疗从而改善患者预后。
Abstract	Trastuzumab, thefirstmonoclonal antibody targeting Human Epidermal Growth Factor Receptor 2 (HER2) hasimprovedthetreatment effect andprognosis of patients with HER2-positive breast cancer and gastric cancer. Trastuzumab has already been the first-line treatment medicine in aforementioned advanced cancers. However, most patients develop acquired resistance after 1 year, resulting in the disease progression. Researches indicate that there are multiple mechanisms mediating trastuzumab resistance such as the change of HER2 protein structure, activation of signaling pathways among other members of HER Family and their ligands, changes of downstream PI3K signaling pathway, epithelial-mesenchymal transition, antibody-dependent cell-mediated cytotoxicity(ADCC) and so on. In this review, we summarize the mechanisms of trastuzumab resistance, in order to provide predictive biomarkers and overcome resistance of trastuzumab therapy. Furthermore, we hope to find more effective targeted drugs or combination therapies.
关键词	曲妥珠单抗耐药；HER2；PI3K信号通路；EMT；ADCC
KeyWord	Trastuzumab Resistance; HER2; PI3K; EMT; ADCC
基金项目
页码	19-24

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引用本文

邢一舒,王赛琪,吕慧芳,聂彩云,王建正,赵慧晨,陈小兵*. 曲妥珠单抗耐药机制研究进展 [J]. 国际临床研究杂志. 2022; 6; (2). 19 - 24.

文献评论

赖**南方医科******

2025-10-04 11:03:12

HER2靶向治疗是精准医疗的重要方向之一，而耐药问题一直是临床治疗效果受限的关键瓶颈，因此本研究具有明确的临床指导意义，选题合理。该刊发表周期较快。建议作者以后增强机制整合与图示表达，发表更高级别期刊杂志。

高**常州市第****** 已认证✔

2025-07-22 01:51:37

该文系统综述了HER2靶向药物曲妥珠单抗的耐药机制，包括HER2蛋白结构改变、HER家族信号通路异常激活、PI3K通路变异、EMT及ADCC作用减弱等关键分子机制。该综述内容翔实，逻辑清晰，不仅总结了当前耐药研究的核心进展，还提出了潜在的生物标志物和联合治疗策略，对临床优化HER2阳性肿瘤患者的个体化治疗具有重要参考价值。

靳**郑州大学****** 已认证✔

2025-07-19 08:22:08

该文围绕曲妥珠单抗在HER2阳性乳腺癌和胃癌治疗中出现耐药的问题展开综述，选题紧扣临床热点，具有较强的现实意义和研究价值。HER2靶向治疗是当前精准医疗的重要方向之一，而耐药问题一直是临床治疗效果受限的关键瓶颈，因此本研究具有明确的临床指导意义，选题具备充分的合理性。文章整体结构清晰，内容安排合理。作者从HER2结构改变、下游信号通路（如PI3K/Akt）异常激活、其他HER家族成员的代偿性激活、上皮-间质转化（EMT）、免疫抑制机制（如ADCP）等多个方面系统总结了曲妥珠单抗的耐药机制，内容覆盖全面，逻辑清楚，层次分明。同时，文中引用了大量中外研究成果，涵盖了从基础实验到临床研究的不同层面，体现出作者对该领域研究动态的较好把握。从科学性角度看，文章论述相对扎实，参考文献来源可靠，包括Cancer Research、Lancet Oncology、Cell等高水平期刊，有助于增强论点的可信度。各类机制之间的关系也有初步的整合性分析，未见明显逻辑错误或过度推论。需要指出的是，文章在机制部分多为文献转述，原创性分析略显薄弱，缺少作者观点的总结或概括性提升，建议在总结与展望中加强批判性思维和未来研究建议的提出。在写作表达方面，语言规范通顺，专业术语使用准确，摘要、中英文关键词、参考文献格式符合学术期刊要求。但全文缺乏图表或路径图等可视化元素，使复杂的分子机制缺乏直观表达。建议作者适当添加一至两幅示意图，概括耐药信号通路或机制框架，以提高可读性和学术吸引力。值得关注的是，该文发表于《国际临床研究杂志》，虽然被CNKI、Google Scholar等数据库收录，但期刊本身为开放获取类新兴刊物，部分机构对其认定尚存争议。该刊发表周期极短（约六周），可能存在快速审稿或编辑流程不严的风险，投稿者应关注其在单位职称评定、科研考核中的认可程度。综上，该文选题合适、综述内容系统详实、引用充分，具备较好的科学性与学术基础，适合用于科技核心层级期刊的综述类文章。但若希望进一步提升质量和学术影响力，建议增强机制整合与图示表达，并考虑选择更具权威性的医学类核心期刊投稿。

h**湖南长沙******

2022-10-30 07:48:39

分析比较全面

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