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经治胃癌患者的药物治疗:当前选择与未来进展

英文原题:Pharmacotherapy for previously treated gastric cancer patients: current options and future developments.

PubMed 2025/08/26(内容时间) Expert Rev Clin Pharmacol Q2 · IF 3.6(JCR 2025)

研究概要

生物标志物驱动的治疗有望在未来成为主流方法。

中文摘要

引言:多项临床试验显示,化疗可延长既往治疗后晚期胃癌(AGC)患者的生存。综述范围:目前,对于既往治疗后的 AGC,疗效已确立的细胞毒药物包括紫杉醇(PTX)、伊立替康(IRI)和曲氟尿苷/替吡嘧啶(FTD/TPI);抗血管内皮生长因子(VEGF)药物 ramucirumab(RAM)也已显示疗效。Pembrolizumab 适用于微卫星高度不稳定(MSI-H)或肿瘤突变负荷(TMB)高的 AGC。对于 HER2 阳性、既往治疗后的 AGC,trastuzumab deruxtecan(T-DXd)已成为首个分子靶向疗法。此外,靶向 claudin-18 亚型 2(CLDN18.2)的抗体疗法已确立为一线治疗,目前有多项后线治疗临床试验正在进行。其他有前景的分子靶点包括滋养层细胞表面抗原 2(TROP2)、细胞质激活/增殖相关蛋白 1(CAPRIN-1)和 KRAS。此外,抗体药物偶联物(ADC)、双特异性抗体(BsAb)和 CAR-T 等创新治疗方法正在开发。本综述总结既往治疗 AGC 的历史及已确立临床试验证据,并讨论正在开展的临床试验和治疗开发未来方向,重点关注靶向治疗。专家观点:生物标志物驱动治疗预计将成为未来主流。

展开英文摘要原文

INTRODUCTION: Several clinical trials have demonstrated that chemotherapy contributes to prolonged survival in patients with previously treated advanced gastric cancer (AGC). AREAS COVERED: Currently, cytotoxic agents with established efficacy for previously treated AGC include paclitaxel (PTX), irinotecan (IRI), and trifluridine/tipiracil (FTD/TPI), while the anti-vascular endothelial growth factor(VEGF) agent ramucirumab (RAM) has also shown efficacy. Pembrolizumab is indicated for AGC with microsatellite instability-high (MSI-H) or high tumor mutational burden (TMB). For human epidermal growth factor receptor 2 (HER2)-positive previously treated AGC, trastuzumab deruxtecan (T-DXd) has emerged as the first molecular targeted therapy. Additionally, claudin-18 isoform 2 (CLDN18.2)-targeting antibody therapy has been established as a first-line treatment, with numerous ongoing clinical trials in later-line settings. Other promising molecular targets include trophoblast cell surface antigen 2 (TROP2), cytoplasmic activation/proliferation-associated protein 1(CAPRIN-1), and KRAS. Furthermore, innovative therapeutic approaches such as antibody-drug conjugates (ADCs), bispecific antibodies (BsAbs), and chimeric antigen receptor T-cell (CAR-T) therapy are being developed. This review summarizes the historical and established evidence from clinical trials on previously treated AGC and discusses ongoing clinical trials and future perspectives in treatment development, with a focus on targeted therapies. EXPERT OPINION: Biomarker-driven treatment is expected to become the mainstream approach in the future.

论文信息

作者
Sato S、Nakayama I、Shitara K
单位
Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.Japan
文献类型
综述
期刊
Expert review of clinical pharmacology2025 Aug
原文标识
PubMed 40853034 · DOI 10.1080/17512433.2025.2551748