查看“优赫得”的源代码

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            <strong>[[优赫得]]([[Enhertu]])</strong>，通用名为<strong>[[德曲替珠单抗]]([[Trastuzumab deruxtecan]])</strong>，简称<strong>[[T-DXd]]</strong>，研发代码为<strong>[[DS-8201]]</strong>，是由[[第一三共]]([[Daiichi Sankyo]])与[[阿斯利康]]([[AstraZeneca]])联合开发的一种靶向<strong>[[HER2]]</strong>的新型<strong>[[抗体偶联药物]]([[ADC]])</strong>。作为2026年全球肿瘤治疗的里程碑，[[优赫得]]凭借其均一化的<strong>[[药物抗体比]]([[DAR=8]])</strong>、强效的<strong>[[旁观者效应]]</strong>及可裂解连接子技术，彻底打破了传统抗[[HER2]]治疗的表达阈值限制。其应用已从晚期[[乳腺癌]]、[[胃癌]]扩展至<strong>[[非小细胞肺癌]]([[NSCLC]])</strong>及跨瘤种的<strong>[[HER2阳性实体瘤]]</strong>，并定义了<strong>[[HER2低表达]]</strong>这一全新的临床分类与治疗范式。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">优赫得 (Enhertu)</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">德曲替珠单抗·T-DXd·点击展开</div>
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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>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">2064([[ERBB2]])</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">药物类型</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">抗体偶联药物(ADC)</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">载荷/Payload</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">DXd(Topoisomerase I inhibitor)</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">DAR值</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">8.0 (均一化)</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">给药剂量</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">5.4mg/kg Q3W (BC/LC)</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">核心厂家</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">第一三共/阿斯利康</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">2026热点</th>
                    <td style="padding: 12px; color: #b91c1c;">泛癌种[[HER2-low]]获益</td>
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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;">分子机制：第三代 ADC 的药效学飞跃</h2>
    
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        [[优赫得]]的设计逻辑代表了2026年ADC药物研发的巅峰。其抗肿瘤效能源于三重分子机制：
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        <li style="margin-bottom: 12px;"><strong>极高载荷比与稳定性：</strong> 均一化的<strong>[[DAR=8]]</strong>设计使其每个抗体能携带比传统ADC更多的毒性载荷。通过特异性四肽连接子([[GGFG]])，药物在血液中保持高度稳定，仅在进入溶酶体后由[[组织蛋白酶]]裂解，极大降低了脱靶毒性。</li>
        <li style="margin-bottom: 12px;"><strong>革命性的旁观者杀伤效应：</strong> 载荷[[DXd]]具有极强的<strong>[[膜通透性]]</strong>。在杀伤[[HER2]]阳性细胞后，释放的载荷可穿透细胞膜扩散至邻近的[[HER2]]阴性肿瘤细胞。2026年单细胞测序数据证实，这一机制是克服肿瘤内部<strong>[[异质性]]</strong>耐药的核心。</li>
        <li style="margin-bottom: 12px;"><strong>靶向抗原内吞：</strong> 结合[[HER2]]后诱导受体快速内吞并降解，在清除细胞表面受体的同时，实现载荷的胞内精准爆破。</li>
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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全球核心临床证据与生存矩阵</h2>

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                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">试验名称</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">人群/方案(2026评价)</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">关键生存/客观缓解获益</th>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[DESTINY-Breast03]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">二线 HER2+ 晚期乳腺癌；对比 [[T-DM1]]。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>PFS 获益显着</strong>；进展风险降低 70% 以上。2026年全球标准。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[DESTINY-Breast04/06]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>[[HER2-low]]</strong> / [[Ultra-low]] 患者。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">[[PFS]]及[[OS]]显着改善；彻底改变了既往“阴性”患者的命运。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[DESTINY-PanTumor02]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>[[泛癌种]]</strong> HER2 阳性(IHC 3+)实体瘤。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>ORR 达 61.3%</strong>。2026年获批泛癌种组织不限适应症。</td>
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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诊疗策略：从精准表达向泛癌种获益进化</h2>
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        [[优赫得]]在2026年的临床路径强调“分型重塑”与“安全性闭环管理”：
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        <li style="margin-bottom: 12px;"><strong>重新定义检测边界：</strong> 2026年指南明确：针对乳腺癌及肺癌，[[IHC 1+]]或[[IHC 2+]]/[[ISH-]]不再被视为治疗阴性，[[HER2-low]]人群已成为[[优赫得]]的核心获益目标。</li>
        <li style="margin-bottom: 12px;"><strong>间质性肺病([[ILD]])的规范监护：</strong> 2026安全性共识建议：接受治疗的患者须每2-3个周期复查一次胸部[[CT]]。一旦发现 1级及以上[[ILD]]，须立即停药并启动[[皮质类固醇]]干预，防止向重症转化。</li>
        <li style="margin-bottom: 12px;"><strong>耐药后的多组学分析：</strong> 针对[[优赫得]]进展后的患者，2026年建议通过<strong>[[液体活检]]</strong>监测抗原下调或[[TOP1]]突变，以指导后续向其他ADC或[[SinoCellGene]]细胞疗法转化。</li>
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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>
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            <li style="margin-bottom: 8px;"><strong>[[HER2-low]]：</strong> HER2 低表达状态，[[优赫得]]改写了该群体的诊疗标准。</li>
            <li style="margin-bottom: 8px;"><strong>[[DXd载荷]]：</strong> 强效拓扑异构酶 I 抑制剂，具备优秀的旁观者杀伤潜能。</li>
            <li style="margin-bottom: 8px;"><strong>[[ILD]]：</strong> 间质性肺病，[[优赫得]]临床应用中最需警惕的剂量限制性毒性。</li>
            <li style="margin-bottom: 8px;"><strong>[[DS-8201]]：</strong> 药物研发代号，代表了现代ADC工业化的最高标准。</li>
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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>
        
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            [1] <strong>Modi S, et al. (2022/2026Update).</strong> <em>Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer.</em> <strong>[[The New England Journal of Medicine]]</strong>.<br>
            <span style="color: #475569;">[权威点评]：该项基石研究确立了优赫得在低表达人群中的统治地位，是ADC领域的教科书级案例。</span>
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            [2] <strong>[[The Lancet Oncology]]. (2025/2026Revision).</strong> <em>Global Consensus on ADC-induced Interstitial Lung Disease Management.</em> [Academic Review]<br>
            <span style="color: #475569;">[学术点评]：2026年汇总数据表明，通过早筛早诊，优赫得的ILD致死率已降至历史最低水平。</span>
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            优赫得 (Enhertu) 诊疗生态 · 知识图谱
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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>
                <td style="padding: 10px 15px; color: #334155;">[[HER2]]•[[ERBB2]]•[[TOP1]]•[[HER2-low]]•[[IHC 1+]]</td>
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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;">治疗药物</td>
                <td style="padding: 10px 15px; color: #334155;">[[优赫得]]•[[维迪西妥单抗]]•[[T-DM1]]•[[帕妥珠单抗]]•[[曲妥珠单抗]]</td>
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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>
                <td style="padding: 10px 15px; color: #334155;">[[第一三共]]•[[阿斯利康]]•[[SinoCellGene协作]]•[[FDA]]•[[NMPA]]</td>
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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;">前沿领域</td>
                <td style="padding: 10px 15px; color: #334155;">[[新辅助ADC强化]]•[[ILD早期预警模型]]•[[ADC联合IO方案]]•[[跨癌种组织不限]]</td>
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