陈雅勤,李海萍

抗体偶联药物（ADC）作为一种新型靶向治疗策略，在肿瘤治疗中展现了显著的潜力。RC48（Disitamab Vedotin）是一种以抗HER-2抗体为基础的ADC药物，已在HER-2阳性胃癌及尿路上皮癌等领域取得突破性进展。近年来，研究发现HER-2在宫颈癌尤其是中晚期患者中的表达具有一定的临床意义，为RC48在该领域的应用提供了理论依据。本综述围绕HER-2在中晚期宫颈癌中的表达特征、RC48的作用机制及其在临床研究中的最新进展展开。首先，分析HER-2在宫颈癌组织中的表达分布及其对疾病进展和预后的影响；其次，阐述RC48通过特异性识别HER-2并释放毒素分子介导肿瘤细胞凋亡的分子机制；最后，总结国内外针对RC48在中晚期宫颈癌治疗中的临床研究数据，包括疗效、安全性及耐受性评价。

抗体偶联药物；RC48；HER-2；中晚期宫颈癌；靶向治疗

[1] 孙小霞,王榆平,思美丽,等.1990—2019年我国宫颈癌发病与死亡趋势及其年龄-时期-队列模型[J].中国癌症防治杂志,2024,16(03):317-320. [2] SINGH D,VIGNAT J,LORENZONI V,et al.Global estimates of in⁃cidence and mortality of cervical cancer in 2020:a baseline analy⁃sis of the WHO Global Cervical Cancer Elimination Initiative[J]. Lancet Glob Health,2023,11(2):e197-e206. [3] 姜丹凤,朱孟秀,赵清娟,等.中国女性生殖系统肿瘤发病率和死亡率分析[J].现代肿瘤医学,2023,31(23):4426⁃4431. [4] 李宏,高蓓,王媛.1990—2019年我国宫颈癌疾病负担变化趋势分析[J].中国慢性病预防与控制,2022,30(9):672⁃675. [5] 于洗河,张景茹,降海蕊,等.中国女性1990—2019年宫颈癌和乳腺癌疾病负担分析[J].中国公共卫生,2022,38(5):534⁃538. [6] 谭勇,彭晶晶,程朋.同步放化疗治疗中晚期宫颈癌的临床疗效观察[J].中国医院用药评价与分析,2010,10(10):918-920. [7] 徐玉怡,曹锦雪,王东凯.抗体偶联药物在肿瘤治疗中的研究进展[J].中国药剂学杂志(网络版),2024,22(03):107-113. [8] TarantinoP,Carmagnani PestanaR,CortiC,et al.Antibody-drug conjugates:Smart chemotherapy delivery across tumor his⁃tologies[J]. CA Cancer J Clin,2022,72(2):165-182. [9] Suzuki M,Yagishita S,Sugihara K,et al.Visualization of intratumor pharmacokinetics of[fam-]trastuzumab deruxte can(DS-8201a)in HER2 heterogeneous model using phosphor-integrated dots imaging analysis.Clin Cancer Res.2021;27:3970-3979. [10] Buckel,L.et al.Tumor radiosensitization by monomethyl auristatin E:mechanism of action and targeted delivery.Cancer Res.75,1376-1387(2015). [11] Hamblett,K.J.et al.Effects of drug loading on the antitumor activity of a monoclonal antibody drug conjugate.Clin.Cancer Res.10, 7063-7070(2004). [12] Adams S R,Yang H C,Savariar E N,et al.Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize[J].Nature communications,2016,7(1):13019. [13] 李科翰,黄文斌,朱雪琼.人表皮生长因子受体2基因在妇科恶性肿瘤中的研究进展[J].浙江医学,2022,44(17):1901-1904+1910. [14] 郎宾,李会荣,朱玉珍.Her-2蛋白在宫颈癌组织中的表达及其临床意义[J].海南医学院学报,2013,19(4):446-448. [15] 张芳,史敏,周成敏,等.宫颈微偏腺癌六例伴五例卵巢转移的临床病理学分析[J].中华病理学杂志,2021,50(2):134-136. [16] Shi H,Shao Y,Lu W,et al.An analysis of HER2 amplification in cervical adenocarcinoma:correlation with clinical outcomes and the international endocervical adenocarcinoma criteria and classification[J].J Pathol Clin Res,2021,7(1):86-95. [17] 孙新超.Her-2蛋白在宫颈癌组织中的表达及其临床意义[J].中国现代药物应用,2016,10(14):38-39. [18] Xiang L,Jiang W,Ye S,et al.ERBB2 mutation:a promising target in non-squamous cervical cancer[J].Gynecol Oncol,2018,148(2):311-316. [19] A.I.Ojesina,L.Lichtenstein,S.S.Freeman,et al.,Landscape of genomic alterations in cervical carcinomas,Nature 506(7488)(2014)371-375. [20] T.K.Chung,P.Van Hummelen,P.K.Chan,et al,Genomic aberrations in cervical ad-enocarcinomas in Hong Kong Chinese women,Int.J. Cancer 137(4)(2015)776–783. [21] Martinho O,Silva-Oliveira R,Cury FP,et al.HER family re-ceptors are important theranostic biomarkers for cervical can⁃cer: blocking glucose metabolism enhances the therapeutic ef⁃fect of HER inhibitors[J].Theranostics,2017,7(3):717-732. [22] 全慧霞,林仲秋.妇科肿瘤人表皮生长因子受体2相关研究进展及检测方法[J].中国实用妇科与产科杂志,2024,40(01):74-84. [23] Xu M,Chen R,Xing P,et al.A multicenter,phase II trial of RC48-ADC combined with radiotherapy,PD-1/PD-L1 inhibitor,GM-CSF,and sequential IL-2(PRaG3.0 regimen)for salvage therapy in patients with HER2-expressing advanced solid tumors[J].J Clin Oncol,2023, 41(16_suppl):e14614-e14614. [24] Lingying W,Guiling L.342 Evaluation of the effectiveness and safety of disitamab vedotin for HER2-expressing recurrent cer-vical cancer after progression on platinum-based treatment-a single-arm,multicenter,open-label,phaseⅡclinical study[J].Int J Gynecologic Cancer,2024.34(Suppl 1):A6. [25] Tagawa ST,Balar AV,Petrylak DP,et al.TROPHY-U-01:a phase II openlabel study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors.J Clin Oncol.2021;39:2474-2485. [26] Coleman RL,Lorusso D,Gennigens C,et al.Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer(innovaTV 204/GOG-3023/ENGOT-cx6):a multicentre, open-label,single-arm,phase 2 study.Lancet Oncol.2021;22(5):609-619. [27] Tarantino P,Ricciuti B,Pradhan SM,et al.Optimizing the safety of antibody-drug conjugates for patients with solid tu-mours[J].Nat Rev Clin Oncol,2023,20(8):558-576. [28] Tolaney,S.M.et al.Adjuvant trastuzumab emtansine versus paclitaxel in combination with trastuzumab for stage I HER2-positive breast cancer(ATEMPT):a randomized clinical trial.J.Clin.Oncol.39,2375-2385(2021). [29] Barroso-Sousa,R.et al.Cardiac outcomes of subjects on adjuvant trastuzumab emtansine vs paclitaxel in combination with trastuzumab for stage I HER2-positive breast cancer(ATEMPT) study (TBCRC033):a randomized controlled trial.NPJ Breast Cancer 8,18(2022). [30] Xu M,Chen R,Xing P,et al.A multicenter,phaseⅡtrial of RC48-ADC combined with radiotherapy,PD-1/PD-L1 inhibi-tor, GM-CSF,and sequential IL-2(PRaG3.0 regimen)for sal⁃vage therapy in patients with HER2-expressing advanced solid tumors[J].J Clin Oncol,2023, 41(16 suppl):e14614.

点击下载PDF