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晚期胃腺癌 - 版本历史
2026-04-18T18:44:56Z
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2026-01-07T01:55:31Z
<p>建立内容为“<div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff…”的新页面</p>
<p><b>新页面</b></p><div><div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff; max-width: 1200px; margin: auto;"><br />
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<strong>[[晚期胃腺癌]]([[Advanced Gastric Adenocarcinoma]])</strong>，指起源于胃黏膜上皮且发生局部浸润不可切除、区域淋巴结广泛转移或远处器官转移的恶性肿瘤。在2026年的精准医学框架下，晚期胃腺癌已不再视作单一疾病，而是基于<strong>[[TCGA分子分型]]</strong>（如[[EBV]]型、[[MSI]]型、[[GS]]型、[[CIN]]型）进行个体化管理的异质性集合。治疗决策核心已从传统化疗全面转向以<strong>[[HER2]]</strong>、<strong>[[Claudin 18.2]]</strong>及<strong>[[PD-L1]]</strong>表达水平为核心的“靶向联合免疫”模式。2026年，随着<strong>[[ADC]]</strong>药物和<strong>[[双特异性抗体]]</strong>的普及，AGA的生存获益已由月度跨越向年度跨越转变。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">晚期胃腺癌</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Advanced Gastric Adenocarcinoma·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;">Gastric Adenocarcinoma Glandular Differentiation (H&E)</div><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心分子靶标：[[HER2]]•[[CLDN18.2]]</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%;">[[Entrez]]ID</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">2064([[ERBB2]])</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[HGNC]]编号</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">3430([[HER2关联]])</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[UniProt]]</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P04626 / P56856</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">药物分子量</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">单抗约145-150kDa</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">ICD-11编码</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;">标志物评估</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[PD-L1 CPS]]•[[MSI]]</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">2026一线标配</th><br />
<td style="padding: 12px; color: #1e40af;">NGS多基因+IHC</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：分子驱动与逃逸路径</h2><br />
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晚期胃腺癌的进展受多种遗传变异与表观遗传调控。2026年的分子解析将其机制归纳为：<br />
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<li style="margin-bottom: 12px;"><strong>HER2 通路异常激活：</strong> <br />
在约15%-20%的[[AGA]]患者中存在<strong>[[ERBB2]]</strong>扩增。HER2受体同源或异源二聚化通过激活<strong>[[PI3K/Akt]]</strong>及<strong>[[MAPK]]</strong>通路，诱导细胞无限增殖及抗凋亡。</li><br />
<li style="margin-bottom: 12px;"><strong>Claudin 18.2 紧密连接重塑：</strong> <br />
作为胃黏膜紧密连接蛋白，<strong>[[CLDN18.2]]</strong>在AGA中由于极性丧失而异常暴露在细胞表面，成为精准打击的理想靶点。2026年证据显示其在弥漫型胃癌中表达率极高。</li><br />
<li style="margin-bottom: 12px;"><strong>免疫逃逸机制：</strong> <br />
通过上调<strong>[[PD-L1]]</strong>或存在<strong>[[dMMR/MSI-H]]</strong>特征，AGA细胞通过抑制[[CD8+T细胞]]活性实现免疫逃逸。2026年的研究重点转向针对[[TKI]]耐药后诱导的<strong>[[FGFR2b]]</strong>过表达逃逸路径。</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 AGA 精准诊疗决策矩阵</h2><br />
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<th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">分子/分型特征</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">2026 一线标准治疗方案</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>+PD-1联合化疗，后线优选<strong>[[T-DXd]]</strong>。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">[[KEYNOTE-811]]：五年生存数据。</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>联合[[mFOLFOX6]]或[[CAPOX]]。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">[[SPOTLIGHT]]研究：显著提升[[PFS]]。</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;"><strong>[[帕博利珠单抗]]</strong> 或 <strong>[[斯鲁利单抗]]</strong>单药/联合方案。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">[[KEYNOTE-158]]：AGA人群长效响应。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">FGFR2b 过表达</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">[[贝马瑞妥单抗]]联合化疗。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">[[FIGHT研究]]：精准靶向新突破。</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;">2026 治疗策略：从全程管理到转化突破</h2><br />
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2026年AGA的管理已进入“动态分子画像”时代，临床路径强调：<br />
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<li style="margin-bottom: 12px;"><strong>转化治疗的地位提升：</strong> 针对初诊不可切除但具有转化潜力的局部晚期AGA，2026版指南建议使用强效靶免联合化疗进行<strong>[[转化治疗]]</strong>，以期实现R0切除并获得<strong>[[pCR]]</strong>。</li><br />
<li style="margin-bottom: 12px;"><strong>ADC 药物的垂直应用：</strong> 针对HER2阳性进展患者，<strong>[[德曲妥珠单抗]]([[T-DXd]])</strong>已正式跨入二线标准治疗。2026年，针对[[Claudin 18.2]]及[[TROP2]]的ADC药物已全面覆盖三线及以上拯救治疗。</li><br />
<li style="margin-bottom: 12px;"><strong>维持治疗策略：</strong> 一线化免方案获最大缓解后，采用<strong>[[氟尿嘧啶]]</strong>类药物联合<strong>[[PD-1]]</strong>抑制剂进行长程维持，已成为延长晚期OS的共识。</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>[[PD-L1 CPS评分]]：</strong> 决定AGA免疫治疗获益程度的关键病理量化指标。</li><br />
<li style="margin-bottom: 8px;"><strong>[[液体活检]]：</strong> 利用<strong>[[ctDNA]]</strong>动态监测晚期患者耐药克隆演变。</li><br />
<li style="margin-bottom: 8px;"><strong>[[印戒细胞癌]]：</strong> AGA中侵袭性最强、对化疗最不敏感的弥漫性组织学亚型。</li><br />
<li style="margin-bottom: 8px;"><strong>[[合成致死]]：</strong> 针对[[DDR]]缺失型AGA的前沿药研方向。</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 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]：该项经典研究确立了AGA免疫治疗时代的开端。</span><br />
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[2] <strong>Shitara K, et al. (2024/2025Revision).</strong> <em>Zolbetuximab plus CAPOX in Claudin 18.2-positive gastric or gastro-oesophageal junction adenocarcinoma: 2026 Integrative Meta-Analysis.</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的靶向干预在AGA治疗中具有显著的独立获益价值。</span><br />
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晚期胃腺癌 (AGA) · 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]]•[[VEGFR2]]•[[TROP2]]</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;">[[曲妥珠单抗]]•[[佐妥昔单抗]]•[[纳武利尤单抗]]•[[德曲妥珠单抗]]•[[阿帕替尼]]</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;">诊断技术</td><br />
<td style="padding: 10px 15px; color: #334155;">[[NGS检测]]•[[PD-L1伴随诊断]]•[[PET-CT]]•[[腹腔镜分期]]</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;">研究机构</td><br />
<td style="padding: 10px 15px; color: #334155;">[[CSCO]]•[[ASCO]]•[[ESMO]]•[[SinoCellGene]]•[[MSKCC]]</td><br />
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223.160.138.166