抗体药物偶联物在人表皮生长因子受体2低表达胃癌中的应用研究进展

doi:10.12114/j.issn.1007-9572.2023.0319

中国全科医学 ›› 2024, Vol. 27 ›› Issue (18): 2287-2294.DOI: 10.12114/j.issn.1007-9572.2023.0319

抗体药物偶联物在人表皮生长因子受体2低表达胃癌中的应用研究进展

康殷楠¹^,², 石嘉琪¹^,², 王俊科¹, 李斌¹, 李初谊¹, 马俊³, 于晓辉¹^,²^,^*()

1．730050　甘肃省兰州市，中国人民解放军联勤保障部队第九四〇医院消化内科二区
2．730000　甘肃省兰州市，甘肃中医药大学第一临床医学院
3．730050　甘肃省兰州市，中国人民解放军联勤保障部队第九四〇医院基础医学实验室　甘肃省干细胞与基因药物重点实验室

收稿日期:2023-05-31 修回日期:2023-07-01 出版日期:2024-06-20 发布日期:2024-03-22
通讯作者: 于晓辉
作者贡献：
康殷楠负责文章构思与设计、论文撰写；石嘉琪、王俊科、李斌、李初谊负责数据整理、表格的编辑；马俊、于晓辉负责论文的审校及修订，提供资金支持。
基金资助:
甘肃省青年科技基金计划(21JR7RA010); 甘肃省非感染性肝病临床医学研究中心(21JR7RA017)

Advances in the Application of Antibody Drug Conjugate in Gastric Cancer with Low Expression of Human Epidermal Growth Factor Receptor 2

KANG Yinnan¹^,², SHI Jiaqi¹^,², WANG Junke¹, LI Bin¹, LI Chuyi¹, MA Jun³, YU Xiaohui¹^,²^,^*()

1. Department of Gastroenterology, 940th Hospital, PLA Joint Logistic Support Force, Lanzhou 730050, China
2. The First Clinical Medical College of Gansu University of Chinese Medicine, Lanzhou 730000, China
3. Basic Medical Laboratory of 940th Hospital of the Joint Logistics Support Force of the People's Liberation Army of China/Gansu Provincial Key Laboratory of Stem Cells and Gene Drugs, Lanzhou 730050, China

Received:2023-05-31 Revised:2023-07-01 Published:2024-06-20 Online:2024-03-22
Contact: YU Xiaohui

分享到

摘要/Abstract

摘要： 胃癌（GC）是极具异质性和侵袭性的消化系统恶性肿瘤之一，传统化疗药物及曲妥珠单抗等人表皮生长因子受体2（HER2）靶向药物在GC的治疗过程中仍然存在耐药性发生率高、毒副作用大、患者耐受差等缺点。因此，研发更为有效的抗GC药物势在必行。目前针对HER2的新型靶向药层出不穷，但在某些情况下无效或产生耐药，这与HER2在某些GC细胞中低表达有关，HER2低表达（HER2 IHC1+或IHC2+/ISH-）约占全部类型的40%~60%，但在临床实践中，这类患者仍被报告为HER2阴性GC。因此准确检测HER2表达状态对于确定可能受益于曲妥珠单抗治疗的患者至关重要。抗体药物偶联物（ADC）的出现为HER2阳性GC提供了新的治疗选择，凭借其精准高效的抗肿瘤作用，有望在未来替代传统GC化学疗法。近期有研究发现ADC可能在HER2低表达GC中具有潜在抗肿瘤活性，相关临床研究正在评估其在HER2低表达GC治疗中的有效性和安全性。本文就靶向治疗时代ADC在HER2低表达GC患者中的应用和最新研究进展作一综述，并讨论HER2靶向ADC在应用和研发过程中面临的挑战。

关键词: 胃肿瘤, 胃癌, 人表皮生长因子受体2, HER2低表达胃癌, 抗体药物偶联物, 分子靶向治疗, 综述

Abstract:

Gastric cancer (GC) is one of the most heterogeneous and aggressive malignant tumors of the digestive system. Traditional chemotherapy drugs and epidermal growth factor receptor 2 (HER2) targeted drugs such as Trastuzumab still have the disadvantages of high incidence of drug resistance, high toxic side effects and poor tolerance of patients. Therefore, it is imperative to develop more effective anti GC drugs. Novel targeted drugs against HER2 are currently available, but are ineffective or resistance in some cases, which is related to the low expression of HER2 (HER2 IHC1+ or IHC2+/ISH-) in certain GC cells, accounting for about 40%-60% of all types. However, in clinical practice, these patients are still reported as HER2-negative GC. Therefore, accurate detection of HER2 expression is crucial to identify patients who may benefit from trastuzumab therapy. The emergence of antibody drug conjugates (ADC) provides a new therapeutic option for HER2-positive GC and it is expected to replace traditional GC chemotherapy in the future by its precise and efficient anti-tumor effect. Recent studies have found that ADC may have potential anti-tumor activity in HER2 low-expression GC, and related clinical studies are evaluating its effectiveness and safety in HER2 low-expression GC treatment. This article reviews the application and the latest research progress of ADC in HER2 low-expression GC patients in the era of targeted therapy and discusses the challenges faced in the application and development of HER2-targeted ADCs.

Key words: Stomach neoplasms, Gastric cancer, Human epidermal growth factor receptor 2, Low expression of HER2 in gastric cancer, Antibody drug conjugates, Molecular targeted therapy, Review

中图分类号:

R 735.2

康殷楠,石嘉琪,王俊科,等. 抗体药物偶联物在人表皮生长因子受体2低表达胃癌中的应用研究进展[J]. 中国全科医学, 2024, 27(18): 2287-2294. DOI: 10.12114/j.issn.1007-9572.2023.0319.
KANG Yinnan,SHI Jiaqi,WANG Junke, et al. Advances in the Application of Antibody Drug Conjugate in Gastric Cancer with Low Expression of Human Epidermal Growth Factor Receptor 2[J]. Chinese General Practice, 2024, 27(18): 2287-2294. DOI: 10.12114/j.issn.1007-9572.2023.0319.

图/表 2

参考文献 54

[1]	LONDON M，GALLO E. Epidermal growth factor receptor（EGFR）involvement in epithelial-derived cancers and its current antibody-based immunotherapies[J]. Cell Biol Int，2020，44（6）：1267-1282. DOI：10.1002/cbin.11340.
[2]	YU J F，FANG T，YUN C Y，et al. Antibody-drug conjugates targeting the human epidermal growth factor receptor family in cancers[J]. Front Mol Biosci，2022，9：847835. DOI：10.3389/fmolb.2022.847835.
[3]	GRAVALOS C，JIMENO A. HER2 in gastric cancer：a new prognostic factor and a novel therapeutic target[J]. Ann Oncol，2008，19（9）：1523-1529. DOI：10.1093/annonc/mdn169.
[4]	ZHOU L，XU H Y，Li S M，et al. Study RC48-C014：Preliminary results of RC48-ADC combined with toripalimab in patients with locally advanced or metastatic urothelial carcinoma[J]. Journal of Clinical Oncology，2022，40（6_suppl）：515. DOI：10.1200/jco.2022.40.6_suppl.515.
[5]	ZHANG L L，HAMDANI O，GJOERUP O，et al. ERBB2 copy number as a quantitative biomarker for real-world outcomes to anti-human epidermal growth factor receptor 2 therapy in advanced gastroesophageal adenocarcinoma[J]. JCO Precis Oncol，2022，6：e2100330. DOI：10.1200/PO.21.00330.
[6]	AJANI J A，D'AMICO T A，BENTREM D J，et al. Gastric cancer，version 2.2022，NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw，2022，20（2）：167-192. DOI：10.6004/jnccn.2022.0008.
[7]	YUN T，WANG S N，JIANG B，et al. Significance of detection of the HER2 gene and PD-1/PD-L1 in gastric cancer[J]. J Oncol，2020，2020：8678945. DOI：10.1155/2020/8678945.
[8]	YANG T，XU R，YOU J H，et al. Prognostic and clinical significance of HER-2 low expression in early-stage gastric cancer[J]. BMC Cancer，2022，22（1）：1168. DOI：10.1186/s12885-022-10262-7.
[9]	KIM C，LEE C K，CHON H J，et al. PTEN loss and level of HER2 amplification is associated with trastuzumab resistance and prognosis in HER2-positive gastric cancer[J]. Oncotarget，2017，8（69）：113494-113501. DOI：10.18632/oncotarget.23054.
[10]	ABDOLLAHPOUR-ALITAPPEH M，LOTFINIA M，GHARIBI T，et al. Antibody-drug conjugates（ADCs）for cancer therapy：strategies，challenges，and successes[J]. J Cell Physiol，2019，234（5）：5628-5642. DOI：10.1002/jcp.27419.
[11]	JIN Y M，EDALATIAN ZAKERI S，BAHAL R，et al. New technologies bloom together for bettering cancer drug conjugates[J]. Pharmacol Rev，2022，74（3）：680-711. DOI：10.1124/pharmrev.121.000499.
[12]	YAGHOUBI S，KARIMI M H，LOTFINIA M，et al. Potential drugs used in the antibody-drug conjugate（ADC）architecture for cancer therapy[J]. J Cell Physiol，2020，235（1）：31-64. DOI：10.1002/jcp.28967.
[13]	中国临床肿瘤学会指南工作委员会组织. 中国临床肿瘤学会（CSCO）胃癌诊疗指南-2022[M]. 北京：人民卫生出版社，2022.
[14]	INDINI A，RIJAVEC E，GROSSI F. Trastuzumab deruxtecan：changing the destiny of HER2 expressing solid tumors[J]. Int J Mol Sci，2021，22（9）：4774. DOI：10.3390/ijms22094774.
[15]	OGITANI Y，AIDA T，HAGIHARA K，et al. DS-8201a，a novel HER2-targeting ADC with a novel DNA topoisomerase Ⅰ inhibitor，demonstrates a promising antitumor efficacy with differentiation from T-DM1[J]. Clin Cancer Res，2016，22（20）：5097-5108. DOI：10.1158/1078-0432.CCR-15-2822.
[16]	OGITANI Y，HAGIHARA K，OITATE M，et al. Bystander killing effect of DS-8201a，a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate，in tumors with human epidermal growth factor receptor 2 heterogeneity[J]. Cancer Sci，2016，107（7）：1039-1046. DOI：10.1111/cas.12966.
[17]	ClinicalTrials.gov. DS-8201a in human epidermal growth factor receptor 2（HER2）-expressing gastric cancer [DESTINY-Gastric01][EB/OL]. （2020-11-27）[2023-04-15].
[18]	YAMAGUCHI K，BANG Y J，IWASA S，et al. 1422MO Trastuzumab deruxtecan（T-DXd；DS-8201）in patients with HER2-low，advanced gastric or gastroesophageal junction（GEJ）adenocarcinoma：results of the exploratory cohorts in the phase Ⅱ，multicenter，open-label DESTINY-Gastric01 study[J]. Ann Oncol，2020，31：S899-900. DOI：10.1016/j.annonc.2020.08.1928.
[19]	YAMAGUCHI K，BANG Y J，IWASA S，et al. Trastuzumab deruxtecan in anti-human epidermal growth factor receptor 2 treatment-naive patients with human epidermal growth factor receptor 2-low gastric or gastroesophageal junction adenocarcinoma：exploratory cohort results in a phaseⅡ trial[J]. J Clin Oncol，2023，41（4）：816-825. DOI：10.1200/JCO.22.00575.
[20]	Phase 2 study of trastuzumab deruxtecan in the neoadjuvant treatment for patients with HER2-positive gastric and gastroesophageal junction adenocarcinoma（EPOC2003）[C]. 2022 ASCO，Abstract TPS4161.
[21]	PENG Z，LIU T S，WEI J，et al. Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing，locally advanced or metastatic gastric or gastroesophageal junction cancer：a single-arm phaseⅡ study[J]. Cancer Commun，2021，41（11）：1173-1182. DOI：10.1002/cac2.12214.
[22]	CHEN Z H，YUAN J J，XU Y Y，et al. From AVATAR mice to patients：RC48-ADC exerted promising efficacy in advanced gastric cancer with HER2 expression[J]. Front Pharmacol，2021，12：757994. DOI：10.3389/fphar.2021.757994.
[23]	LI H W，YU C，JIANG J，et al. An anti-HER2 antibody conjugated with monomethyl auristatin E is highly effective in HER2-positive human gastric cancer[J]. Cancer Biol Ther，2016，17（4）：346-354. DOI：10.1080/15384047.2016.1139248.
[24]	金洋冰，蔡劬，计骏，等. 抗体偶联药物维迪西妥单抗对HER-2不同表达水平胃癌细胞抑制效应的体外研究[J]. 临床肿瘤学杂志，2023，28（1）：1-7. DOI：10.3969/j.issn.1009-0460.2023.01.001.
[25]	ClinicalTrials.gov. Study of RC48-ADC Administered Intravenously to Subjects with HER2-Positive in Advanced Malignant Solid Tumors[EB/OL]. （2020-11-27）[2023-04-15].
[26]	XU Y Y，WANG Y K，GONG J F，et al. PhaseⅠ study of the recombinant humanized anti-HER2 monoclonal antibody-MMAE conjugate RC48-ADC in patients with HER2-positive advanced solid tumors[J]. Gastric Cancer，2021，24（4）：913-925. DOI：10.1007/s10120-021-01168-7.
[27]	国家药品监督管理局. 国家药监局附条件批准注射用维迪西妥单抗上市[EB/OL]. （2021-06-09）[2023-04-15].
[28]	ClinicalTrials.gov. Phase 2 Study of T-DXd in the Neoadjuvant Treatment for Patients with HER2 Positive Gastric and GEJ Adenocarcinoma[EB/OL]. （2020-11-27）[2023-04-15].
[29]	ClinicalTrials.gov. A Study of RC48-ADC in Local Advanced or Metastatic Gastric Cancer Subjects with the Overexpression of HER2[EB/OL]. （2022-01-13）[2023-04-15].
[30]	ClinicalTrials.gov. First-line Treatment with RC48 Plus Tislelizumab and S-1（RCTS）in Advanced Gastric Cancer（RCTS）[EB/OL]. （2022-10-19）[2023-04-15].
[31]	BAROK M，JONCOUR V L，MARTINS A，et al. ARX788，a novel anti-HER2 antibody-drug conjugate，shows anti-tumor effects in preclinical models of trastuzumab emtansine-resistant HER2-positive breast cancer and gastric cancer[J]. Cancer Lett，2020，473：156-163. DOI：10.1016/j.canlet.2019.12.037.
[32]	SKIDMORE L，SAKAMURI S，KNUDSEN N A，et al. ARX788，a site-specific anti-HER2 antibody-drug conjugate，demonstrates potent and selective activity in HER2-low and T-DM1-resistant breast and gastric cancers[J]. Mol Cancer Ther，2020，19（9）：1833-1843. DOI：10.1158/1535-7163.MCT-19-1004.
[33]	BAROK M，JONCOUR V L，MARTINS A，et al. ARX788，a novel anti-HER2 antibody-drug conjugate，shows anti-tumor effects in preclinical models of trastuzumab emtansine-resistant HER2-positive breast cancer and gastric cancer[J]. Cancer Lett，2020，473：156-163. DOI：10.1016/j.canlet.2019.12.037.
[34]	ZHANG Y，QIU M Z，WANG J F，et al. Phase 1 multicenter，dose-expansion study of ARX788 as monotherapy in HER2-positive advanced gastric and gastroesophageal junction adenocarcinoma[J]. Cell Rep Med，2022，3（11）：100814. DOI：10.1016/j.xcrm.2022.100814.
[35]	Clinicaltrials. searchlistdetail. ARX788在HER2阳性晚期胃癌和胃食管连接部腺癌患者中的有效性及安全性研究[EB/OL]. （2021-07-12）[2023-04-15].
[36]	EDUPUGANTI V V S R，TYNDALL J D A T D A，GAMBLE A B. Self-immolative linkers in prodrugs and antibody drug conjugates in cancer treatment[J]. Recent Pat Anticancer Drug Discov，2021，16（4）：479-497. DOI：10.2174/1574892816666210509001139.
[37]	SHIN S H，PARK Y H，PARK S S，et al. An elaborate new linker system significantly enhances the efficacy of an HER2-antibody-drug conjugate against refractory HER2-positive cancers[J]. Adv Sci，2021，8（23）：e2102414. DOI：10.1002/advs.202102414.
[38]	ClinicalTrials.gov. Phase 1 Study of FS-1502 in Patients with HER2 Expressed Advanced Solid Tumors and Breast Cancer[EB/OL]. （2022-05-20）[2023-04-15].
[39]	LI H，ZHANG X，XU Z Y，et al. Preclinical evaluation of MRG002，a novel HER2-targeting antibody-drug conjugate with potent antitumor activity against HER2-positive solid tumors[J]. Antib Ther，2021，4（3）：175-184. DOI：10.1093/abt/tbab017.
[40]	YU J F，FANG T，YUN C Y，et al. Antibody-drug conjugates targeting the human epidermal growth factor receptor family in cancers[J]. Front Mol Biosci，2022，9：847835. DOI：10.3389/fmolb.2022.847835.
[41]	ClinicalTrials.gov. A Study of MRG002 in the Treatment of Patients with HER2-positive Advanced Solid Tumors[EB/OL]. （2021-12-03）[2023-04-15].
[42]	ClinicalTrials.gov. A Study of MRG002 in the Treatment of HER2-positive/HER2-low Locally Advanced or Metastatic Gastric/Gastroesophageal Junction Cancer[EB/OL]. （2022-02-23）[2023-04-15].
[43]	ClinicalTrials.gov. PF-06804103 Dose Escalation in HER2 Positive and Negative（Negative Only in Part 2）Solid Tumors[EB/OL]. （2022-03-18）[2023-04-15].
[44]	ClinicalTrials.gov. A Dose-escalation，Expansion Study of ARX788，in Advanced Solid Tumors Subjects with HER2 Expression（ACE-Pan Tumor 01）[EB/OL]. （2023-04-10）[2023-04-15].
[45]	ClinicalTrials.gov. A Study of MRG002 in Patients with HER2-Positive Advanced Solid Tumors and Locally Advanced or Metastatic Gastric/Gastroesophageal Junction（GEJ）Cancer[EB/OL]. （2022-05-06）[2023-04-15].
[46]	ClinicalTrials.gov. A Study of XMT-2056 in Advanced/Recurrent Solid Tumors That Express HER2[EB/OL]. （2023-03-15）[2023-04-15].
[47]	ClinicalTrials.gov. ISPY-P1.01：Evaluating the Safety of Weekly Paclitaxel with Trastuzumab Duocarmazine（SYD985）in Patients with Metastatic Cancer[EB/OL]. （2023-03-24）[2023-04-15].
[48]	MAHALINGAIAH P K，CIURLIONIS R，DURBIN K R，et al. Potential mechanisms of target-independent uptake and toxicity of antibody-drug conjugates[J]. Pharmacol Ther，2019，200：110-125. DOI：10.1016/j.pharmthera.2019.04.008.
[49]	YU M H，LIANG Y，LI L H，et al. Research progress of antibody-drug conjugates therapy for HER2-low expressing gastric cancer[J]. Transl Oncol，2023，29：101624. DOI：10.1016/j.tranon.2023.101624.
[50]	GARCÍA-ALONSO S，OCAÑA A，PANDIELLA A. Trastuzumab emtansine：mechanisms of action and resistance，clinical progress，and beyond[J]. Trends Cancer，2020，6（2）：130-146. DOI：10.1016/j.trecan.2019.12.010.
[51]	DÍAZ-RODRÍGUEZ E，GANDULLO-SÁNCHEZ L，OCAÑA A，et al. Novel ADCs and strategies to overcome resistance to anti-HER2 ADCs[J]. Cancers，2021，14（1）：154. DOI：10.3390/cancers14010154.
[52]	BON G，PIZZUTI L，LAQUINTANA V，et al. Loss of HER2 and decreased T-DM1 efficacy in HER2 positive advanced breast cancer treated with dual HER2 blockade：the SePHER Study[J]. J Exp Clin Cancer Res，2020，39（1）：279. DOI：10.1186/s13046-020-01797-3.
[53]	GINZEL J D，ACHARYA C R，LUBKOV V，et al. HER2 isoforms uniquely program intratumor heterogeneity and predetermine breast cancer trajectories during the occult tumorigenic phase[J]. Mol Cancer Res，2021，19（10）：1699-1711. DOI：10.1158/1541-7786.MCR-21-0215.
[54]	WANG S，ZHAO Y Z，SONG Y G，et al. ERBB2D16 expression in HER2 positive gastric cancer is associated with resistance to trastuzumab[J]. Front Oncol，2022，12：855308. DOI：10.3389/fonc.2022.855308.

ADC	靶点	治疗方案	试验分组	编号	阶段
T-DXd	HER2	T-DXd或伊立替康/紫杉醇单药	HER2过表达（IHC3+或IHC2+/ISH+） HER2低表达（IHC2+/ISH-或IHC1+）	NCT03329690^[17]	Ⅱ
T-DXd	HER2	T-DXd单药	主要队列：HER2过表达（IHC3+，或IHC2+和ISH+）T-DXd（6.4 mg/kg），1次/3周	NCT05034887^[28]	Ⅱ
		T-DXd单药	探索性队列：HER2低表达（IHC1+或IHC2+和ISH-）T-DXd（6.4 mg/kg），1次/3周
RC48	HER2	RC48单药	RC48（0.1 mg/kg、0.5 mg/kg、1.0 mg/kg、1.5 mg/kg、2.0 mg/kg、2.5 mg/kg、3.0 mg/kg、3.5 mg/kg、4.0 mg/kg）不同剂量增量	NCT02881190^[25]	Ⅰ
RC48	HER2	RC48单药	RC48：2.5 mg/kg，静脉注射，1次/2周	NCT03556345^[29]	Ⅱ
RC48	HER2	RC48联合替雷利珠单抗和S-1	RC48：2.5 mg/kg，第1天，静脉滴注，1次/3周；替雷利珠单抗：200 mg，第1天，静脉滴注，次/3周；S-1：40~60 mg，根据患者体表面积，口服，2次/d，第1~14天，停药7 d	NCT05586061^[30]	Ⅱ

ADC	靶点	治疗方案	试验分组	编号	阶段
T-DXd	HER2	T-DXd或伊立替康/紫杉醇单药	HER2过表达（IHC3+或IHC2+/ISH+） HER2低表达（IHC2+/ISH-或IHC1+）	NCT03329690^[17]	Ⅱ
T-DXd	HER2	T-DXd单药	主要队列：HER2过表达（IHC3+，或IHC2+和ISH+）T-DXd（6.4 mg/kg），1次/3周	NCT05034887^[28]	Ⅱ
		T-DXd单药	探索性队列：HER2低表达（IHC1+或IHC2+和ISH-）T-DXd（6.4 mg/kg），1次/3周
RC48	HER2	RC48单药	RC48（0.1 mg/kg、0.5 mg/kg、1.0 mg/kg、1.5 mg/kg、2.0 mg/kg、2.5 mg/kg、3.0 mg/kg、3.5 mg/kg、4.0 mg/kg）不同剂量增量	NCT02881190^[25]	Ⅰ
RC48	HER2	RC48单药	RC48：2.5 mg/kg，静脉注射，1次/2周	NCT03556345^[29]	Ⅱ
RC48	HER2	RC48联合替雷利珠单抗和S-1	RC48：2.5 mg/kg，第1天，静脉滴注，1次/3周；替雷利珠单抗：200 mg，第1天，静脉滴注，次/3周；S-1：40~60 mg，根据患者体表面积，口服，2次/d，第1~14天，停药7 d	NCT05586061^[30]	Ⅱ

ADC	靶点	抗体	毒素	连接	注册号	人数
ARX788	HER2	曲妥珠单抗	AS269	与pAcF缀合的不可裂解连接子	NCT03255070^[44]	106
					CTR20190639^[34]	22
LCB-ADC	HER2	曲妥珠单抗	MMAF	PEG-3/PEG-3，3，3/PEG-6，6，3	NCT03944499^[38]	297
MRG002	HER2	曲妥珠单抗	MMAE	缬氨酸-瓜氨酸连接子	NCT05141747^[42]	60
					NCT04492488^[45]	129
PF-06804103	HER2	曲妥珠单抗	奥司他汀-0101	缬氨酸-瓜氨酸连接子	NCT03284723^[43]	95
XMT-2056	HER2	曲妥珠单抗/帕妥珠单抗	STING激动剂	—	NCT05514717^[46]	171
SYD985	HER2	曲妥珠单抗	杜卡霉素	vc-seco-DUBA	NCT04602117^[47]	27

ADC	靶点	抗体	毒素	连接	注册号	人数
ARX788	HER2	曲妥珠单抗	AS269	与pAcF缀合的不可裂解连接子	NCT03255070^[44]	106
					CTR20190639^[34]	22
LCB-ADC	HER2	曲妥珠单抗	MMAF	PEG-3/PEG-3，3，3/PEG-6，6，3	NCT03944499^[38]	297
MRG002	HER2	曲妥珠单抗	MMAE	缬氨酸-瓜氨酸连接子	NCT05141747^[42]	60
					NCT04492488^[45]	129
PF-06804103	HER2	曲妥珠单抗	奥司他汀-0101	缬氨酸-瓜氨酸连接子	NCT03284723^[43]	95
XMT-2056	HER2	曲妥珠单抗/帕妥珠单抗	STING激动剂	—	NCT05514717^[46]	171
SYD985	HER2	曲妥珠单抗	杜卡霉素	vc-seco-DUBA	NCT04602117^[47]	27

抗体药物偶联物在人表皮生长因子受体2低表达胃癌中的应用研究进展

Advances in the Application of Antibody Drug Conjugate in Gastric Cancer with Low Expression of Human Epidermal Growth Factor Receptor 2

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

图/表 2

参考文献 54

相关文章 15

编辑推荐

Metrics

留言

[1]	倪嘉淳, 蔡增进, 侯长城, 江琼, 康健, 杨向东, 樊文彬. 痔病评估分类法研究进展及评估价值分析[J]. 中国全科医学, 2024, 27(20): 2545-2550.
[2]	李孟野, 姜一农. 可溶性肾素前体受体在多系统疾病中的研究进展[J]. 中国全科医学, 2024, 27(18): 2295-2300.
[3]	马桂芬, 章倩, 刘娟, 孙菁, 林根来. Ⅲ期胃癌D2根治术后辅助放化疗患者长期预后的影响因素：基于10年随访数据[J]. 中国全科医学, 2024, 27(17): 2091-2097.
[4]	胥梓薇, 程康耀, 桂莉. 突发重大传染病事件背景下过负荷医院管理研究的范围综述[J]. 中国全科医学, 2024, 27(16): 2039-2044.
[5]	倪雪桐, 王若羲, 张晶, 杨兴华. 非酒精性脂肪性肝病、代谢相关脂肪性肝病与心血管疾病关联的国内外研究进展[J]. 中国全科医学, 2024, 27(16): 2033-2038.
[6]	吴美倩, 肖进, 李斐斐, 胡镕镕, 刘彩霞. 24小时活动行为：老年人健康影响因素研究的新方向[J]. 中国全科医学, 2024, 27(15): 1911-1916.
[7]	王芳芳, 朱莉, 幸佳佳, 庞日朝, 苟翔, 张安仁. 创伤性中枢神经系统损伤后肠道屏障变化及其可能机制的研究进展[J]. 中国全科医学, 2024, 27(14): 1775-1781.
[8]	曹佳岑, 张宏坤, 赵文, 南月敏, 李冬冬. 血红素氧合酶1调节铁死亡在非酒精性脂肪性肝病中的研究进展[J]. 中国全科医学, 2024, 27(14): 1782-1788.
[9]	杜书琴, 钱立锋, 熊烈, 史汉强, 石彦波. 铁死亡：抑郁症治疗的新靶点[J]. 中国全科医学, 2024, 27(12): 1417-1423.
[10]	冉东升, 逯艳艳, 辛春玲, 马颖才. 血脂异常与结直肠锯齿状病变、结直肠癌相关性研究进展[J]. 中国全科医学, 2024, 27(12): 1424-1430.
[11]	赵静静, 张志红, 甄俊平. 异柠檬酸脱氢酶基因突变在软骨肉瘤中的研究进展及展望[J]. 中国全科医学, 2024, 27(11): 1400-1404.
[12]	钟锦佳, 李文涛, 黄亚芳, 吴浩. 初级保健领域基于机器学习预测模型研究的设计特征与方法学质量：范围综述[J]. 中国全科医学, 2024, 27(10): 1271-1276.
[13]	温静, 张悦, 梁旭阳, 吕胜祥. 农村上消化道癌机会性筛查分析的胃癌影响因素研究：基于苏北沿海地区[J]. 中国全科医学, 2024, 27(09): 1042-1047.
[14]	王清玉, 林征, 雷阳, 孙彩云, 王咪, 顾珺怡, 朱展慧, 唐李晨. 儿童青少年回避性/限制性摄食障碍：评估与治疗[J]. 中国全科医学, 2024, 27(09): 1028-1033.
[15]	陈玟瑾, 陈飘盈, 杨晓华, 陈轶凡, 蔡业峰, 倪小佳. 膳食模式与脑血管疾病相关的流行病学研究新进展[J]. 中国全科医学, 2024, 27(08): 900-907.