The preclinical discovery and development of zolbetuximab for the treatment of gastric cancer.

IF 6 2区医学 Q1 PHARMACOLOGY & PHARMACY

Expert Opinion on Drug Discovery Pub Date : 2024-08-01 Epub Date: 2024-06-26 DOI:10.1080/17460441.2024.2370332

Yongji Zeng, A Craig Lockhart, Ramon U Jin

{"title":"The preclinical discovery and development of zolbetuximab for the treatment of gastric cancer.","authors":"Yongji Zeng, A Craig Lockhart, Ramon U Jin","doi":"10.1080/17460441.2024.2370332","DOIUrl":null,"url":null,"abstract":"Introduction: Gastric cancer remains a formidable challenge in oncology with high mortality rates and few advancements in treatment. Claudin-18.2 (CLDN18.2) is a tight junction protein primarily expressed in the stomach and is frequently overexpressed in certain subsets of gastric cancers. Targeting CLDN18.2 with monoclonal antibodies, such as zolbetuximab (IMAB362), has shown promising efficacy results in combination with chemotherapy.Areas covered: The molecular cell biology of CLDN18.2 is discussed along with studies demonstrating the utility of CLDN18.2 expression as a biomarker and therapeutic target. Important clinical studies are reviewed, including Phase III trials, SPOTLIGHT and GLOW, which demonstrate the efficacy of zolbetuximab in combination with chemotherapy in patients with CLDN18.2-positive advanced gastric cancer.Expert opinion: CLDN18.2 is involved in gastric differentiation through maintenance of epithelial barrier function and coordination of signaling pathways, and its expression in gastric cancers reflects a 'gastric differentiation' program. Targeting Claudin-18.2 represents the first gastric cancer specific 'targeted' treatment. Further studies are needed to determine its role within current gastric cancer treatment sequencing, including HER2-targeted therapies and immunotherapies. Management strategies will also be needed to better mitigate zolbetuximab-related treatment side effects, including gastrointestinal (GI) toxicities.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.0000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Opinion on Drug Discovery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17460441.2024.2370332","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/26 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction: Gastric cancer remains a formidable challenge in oncology with high mortality rates and few advancements in treatment. Claudin-18.2 (CLDN18.2) is a tight junction protein primarily expressed in the stomach and is frequently overexpressed in certain subsets of gastric cancers. Targeting CLDN18.2 with monoclonal antibodies, such as zolbetuximab (IMAB362), has shown promising efficacy results in combination with chemotherapy.

Areas covered: The molecular cell biology of CLDN18.2 is discussed along with studies demonstrating the utility of CLDN18.2 expression as a biomarker and therapeutic target. Important clinical studies are reviewed, including Phase III trials, SPOTLIGHT and GLOW, which demonstrate the efficacy of zolbetuximab in combination with chemotherapy in patients with CLDN18.2-positive advanced gastric cancer.

Expert opinion: CLDN18.2 is involved in gastric differentiation through maintenance of epithelial barrier function and coordination of signaling pathways, and its expression in gastric cancers reflects a 'gastric differentiation' program. Targeting Claudin-18.2 represents the first gastric cancer specific 'targeted' treatment. Further studies are needed to determine its role within current gastric cancer treatment sequencing, including HER2-targeted therapies and immunotherapies. Management strategies will also be needed to better mitigate zolbetuximab-related treatment side effects, including gastrointestinal (GI) toxicities.

查看原文本刊更多论文

用于治疗胃癌的唑贝妥昔单抗的临床前发现和开发。

前言胃癌仍然是肿瘤学领域的一项艰巨挑战，死亡率高，而治疗方面却鲜有进展。Claudin-18.2（CLDN18.2）是一种主要在胃中表达的紧密连接蛋白，在某些胃癌亚型中经常过度表达。用单克隆抗体（如唑贝妥昔单抗（IMAB362））靶向 CLDN18.2，与化疗联合治疗显示出良好的疗效：讨论了 CLDN18.2 的分子细胞生物学，以及证明 CLDN18.2 表达作为生物标记物和治疗靶点的实用性的研究。回顾了重要的临床研究，包括III期试验 "SPOTLIGHT "和 "GLOW"，这些试验证明了唑贝妥昔单抗联合化疗对CLDN18.2阳性晚期胃癌患者的疗效：CLDN18.2通过维持上皮屏障功能和协调信号通路参与胃分化，它在胃癌中的表达反映了 "胃分化 "程序。以Claudin-18.2为靶点是首个胃癌特异性 "靶向 "治疗方法。还需要进一步研究以确定其在当前胃癌治疗排序中的作用，包括 HER2 靶向疗法和免疫疗法。还需要制定管理策略，以更好地减轻唑贝妥昔单抗相关的治疗副作用，包括胃肠道（GI）毒性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Expert Opinion on Drug Discovery 医学-药学

CiteScore

10.20

自引率

1.60%

发文量

审稿时长

6-12 weeks

期刊介绍： Expert Opinion on Drug Discovery (ISSN 1746-0441 [print], 1746-045X [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on novel technologies involved in the drug discovery process, leading to new leads and reduced attrition rates. Each article is structured to incorporate the author’s own expert opinion on the scope for future development. The Editors welcome: Reviews covering chemoinformatics; bioinformatics; assay development; novel screening technologies; in vitro/in vivo models; structure-based drug design; systems biology Drug Case Histories examining the steps involved in the preclinical and clinical development of a particular drug The audience consists of scientists and managers in the healthcare and pharmaceutical industry, academic pharmaceutical scientists and other closely related professionals looking to enhance the success of their drug candidates through optimisation at the preclinical level.

文献相关原料

公司名称	产品信息	采购帮参考价格