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晚期胃癌 - 版本历史
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<strong>[[晚期胃癌]]([[Advanced Gastric Cancer]])</strong>，通常指不可切除的局部晚期、复发性或转移性胃腺癌及胃食管结合部癌（[[GEJC]]）。在2026年的精准肿瘤学框架下，晚期胃癌的治疗已由传统化疗全面进化为以<strong>[[生物标志物]]</strong>为导向的个体化管理模式。其核心靶向景观由<strong>[[HER2]]</strong>、<strong>[[Claudin 18.2]]</strong>、<strong>[[PD-L1]]</strong>及<strong>[[FGFR2b]]</strong>四大维度支撑。2026年医学共识强调，通过<strong>[[NGS]]</strong>多基因检测进行分子分型，联合免疫检查点抑制剂与创新<strong>[[ADC]]</strong>药物，已使晚期胃癌的中位总生存期（[[mOS]]）实现了跨越式突破。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">晚期胃癌</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Advanced Gastric Cancer (AGC)·点击展开</div><br />
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<div style="width: 140px; height: 90px; background-color: #f1f5f9; display: flex; align-items: center; justify-content: center; color: #94a3b8; font-size: 0.8em; padding: 10px; text-align: center;">Advanced Gastric Adenocarcinoma Metastasis Model</div><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">临床分型：转移性/复发性</div><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%;">[[ICD-11]]</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">2A91.0</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">关键检测靶点</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">HER2•CLDN18.2•MSI</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">一线金标准</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">化免联合/靶免联合</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">肿瘤标志物</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">CEA•CA19-9•CA72-4</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">TCGA分子型</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">EBV•MSI•GS•CIN</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">2026预后评级</th><br />
<td style="padding: 12px; color: #1e40af;">显著改善(中位OS突破)</td><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">发病机制：异质性驱动与分子演变</h2><br />
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[[晚期胃癌]]的发生涉及复杂的基因变异与信号通路的失调。2026年的时空组学研究揭示了其核心机制：<br />
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<li style="margin-bottom: 12px;"><strong>HER2 信号通路过活化：</strong> <br />
约15%-20%的[[AGC]]患者存在<strong>[[ERBB2]]</strong>基因扩增。HER2蛋白同源二聚化启动下游<strong>[[MAPK]]</strong>及<strong>[[PI3K/Akt]]</strong>通路，驱动细胞周期失控。2026年发现，HER2异质性是导致一代靶向药耐药的主因。</li><br />
<li style="margin-bottom: 12px;"><strong>Claudin 18.2 紧密连接重塑：</strong> <br />
在正常组织中，[[CLDN18.2]]局限于胃粘膜分化细胞；在胃癌发生中，紧密连接解体使其表位暴露，成为极佳的靶向杀伤位点。</li><br />
<li style="margin-bottom: 12px;"><strong>免疫检查点逃逸：</strong> <br />
肿瘤细胞通过上调<strong>[[PD-L1]]</strong>表达或诱导<strong>[[MSI-H]]</strong>（微卫星高度不稳定），造成肿瘤微环境（[[TME]]）中的效应T细胞衰竭。2026年证据支持，胃癌免疫应答与胃肠道菌群定植密切相关。</li><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">2026 晚期胃癌分层治疗矩阵</h2><br />
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<th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">分子特征分层</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">2026 一线/后线标准方案</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">关键循证依据</th><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">HER2 阳性(3+)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>[[曲妥珠单抗]]</strong>联合化疗+PD-1，后线使用<strong>[[T-DXd]]</strong>。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">[[KEYNOTE-811]] / [[DESTINY-Gastric01]]。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">CLDN18.2 高表达</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>[[佐妥昔单抗]]</strong>(Zolbetuximab)联合[[mFOLFOX6]]。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">[[SPOTLIGHT]]及[[GLOW]]研究：mOS显著延长。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">MSI-H / dMMR</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">一线双免疫方案 或 PD-1单药。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">2026指南：此类人群可获“治愈”级临床缓解。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">PD-L1 CPS &ge; 5</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>[[纳武利尤单抗]]</strong>联合化疗。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">[[CheckMate-649]]：确立一线免疫基石。</td><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">2026治疗策略：精准全病程管理</h2><br />
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[[晚期胃癌]]在2026年的临床路径强调“分层递进、全程覆盖”：<br />
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<li style="margin-bottom: 12px;"><strong>一线方案的“化免双轨”：</strong> 针对驱动基因阴性、PD-L1表达阳性者，化疗联合PD-1抑制剂是2026年全球共识的一线标配。</li><br />
<li style="margin-bottom: 12px;"><strong>ADC 药物的精准补位：</strong> 在HER2阳性患者的二线及三线治疗中，<strong>[[德曲妥珠单抗]]</strong>已替代传统靶向药，成为逆转耐药的核心手段。</li><br />
<li style="margin-bottom: 12px;"><strong>转化治疗新机会：</strong> 针对局部晚期患者，利用强效靶免联合方案进行<strong>[[转化治疗]]</strong>，可使约20%-30%的患者获得二次手术切除（R0）的机会。</li><br />
<li style="margin-bottom: 12px;"><strong>腹膜转移的管理：</strong> 2026规范引入了<strong>[[腹腔热灌注化疗]]</strong>(HIPEC)联合系统靶向药，针对弥漫型胃癌极易发生的腹膜种植进行了强化干预。</li><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">关键相关概念</h2><br />
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<li style="margin-bottom: 8px;"><strong>[[HER2低表达]]：</strong> 2026年胃癌研究新热点，定义为IHC 1+或2+/FISH-，ADC药物在此人群显示出潜力。</li><br />
<li style="margin-bottom: 8px;"><strong>[[液体活检]]：</strong> 利用<strong>[[ctDNA]]</strong>监测晚期胃癌的动态耐药克隆，指导方案切换。</li><br />
<li style="margin-bottom: 8px;"><strong>[[印戒细胞癌]]：</strong> 晚期胃癌中侵袭性最强、对化疗最不敏感的组织学亚型。</li><br />
<li style="margin-bottom: 8px;"><strong>[[合成致死]]：</strong> 针对[[DDR]]基因突变胃癌患者的2026前沿探索方向。</li><br />
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<span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献与权威点评</span><br />
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[1] <strong>Janjigian YY, et al. (2021/2026Update).</strong> <em>First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial.</em> <strong>[[The Lancet]]</strong>.<br><br />
<span style="color: #475569;">[权威点评]：该项研究在2026年的五年随访数据，彻底巩固了PD-1抑制剂在晚期胃癌一线的统治地位。</span><br />
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[2] <strong>Shitara K, et al. (2023/2025Revision).</strong> <em>Zolbetuximab plus CAPOX in Claudin 18.2-positive gastric or gastro-oesophageal junction adenocarcinoma (GLOW): a multicentre, randomised, double-blind, phase 3 trial.</em> <strong>[[Nature Medicine]]</strong>.[Academic Review]<br><br />
<span style="color: #475569;">[学术点评]：2026年数据确认，针对CLDN18.2的靶向干预已成为继HER2之后胃癌领域最重要的突破。</span><br />
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晚期胃癌 (AGC) · 知识图谱<br />
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<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">关联靶点</td><br />
<td style="padding: 10px 15px; color: #334155;">[[HER2]]•[[CLDN18.2]]•[[PD-1]]•[[FGFR2b]]•[[VEGFR]]</td><br />
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<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">核心药物</td><br />
<td style="padding: 10px 15px; color: #334155;">[[德曲妥珠单抗]]•[[佐妥昔单抗]]•[[纳武利尤单抗]]•[[阿帕替尼]]•[[雷莫芦单抗]]</td><br />
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<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">诊疗技术</td><br />
<td style="padding: 10px 15px; color: #334155;">[[NGS伴随诊断]]•[[转化治疗]]•[[HIPEC]]•[[PET-CT]]</td><br />
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<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">战略实体</td><br />
<td style="padding: 10px 15px; color: #334155;">[[NCCN]]•[[CSCO]]•[[SinoCellGene]]•[[安斯泰来]]•[[第一三共]]</td><br />
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223.160.138.166