查看“依米贝妥单抗”的源代码

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            <strong>[[依米贝妥单抗]]</strong>（<strong>[[Emibetuzumab]]</strong>）是一种创新的、针对<strong>[[肝细胞生长因子受体]]</strong>（<strong>[[MET]]</strong>）的人源化二价<strong>[[单克隆抗体]]</strong>。该药物由[[礼来]]（[[Eli Lilly]]）研发，具备独特的双重抗肿瘤机制：既能阻断配体[[HGF]]与[[MET]]受体的结合，又能诱导[[MET]]受体从细胞表面[[内吞]]并降解。在临床实践中，[[依米贝妥单抗]]主要用于治疗[[MET]]过表达或扩增的<strong>[[非小细胞肺癌]]</strong>（[[NSCLC]]）及<strong>[[胃癌]]</strong>。特别是在克服[[EGFR-TKI]]获得性耐药方面，其通过抑制[[MET]]旁路激活展现了显著的药理价值。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">[[依米贝妥单抗]]</div>
            <div style="font-size: 0.75em; opacity: 0.85; margin-top: 4px;">[[Emibetuzumab]] / [[LY2875358]] · 点击展开</div>
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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;">[[MET]]抗体结合模型示意</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心靶点：[[MET]] ([[HGFR]])</div>
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                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">4233([[MET]])</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[HGNC]]ID</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">7029</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[UniProt]]</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P08581</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">药物类别</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[单克隆抗体]]</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[分子量]]</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">约147kDa</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569;">研发公司</th>
                    <td style="padding: 12px; color: #0f172a;">[[礼来]]([[Eli Lilly]])</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：双重靶向阻断与降解</h2>
    
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        [[依米贝妥单抗]]的设计巧妙结合了“空间位阻”与“生物降解”两种策略，其抗肿瘤效应通过以下路径实现：
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        <li style="margin-bottom: 12px;"><strong>阻断HGF结合：</strong>作为一种二价抗体，[[依米贝妥单抗]]能够高亲和力竞争结合[[MET]]受体的胞外结构域，阻止[[肝细胞生长因子]]（[[HGF]]）诱导的受体[[二聚化]]，从而切断经典的下游[[信号转导]]。</li>
        <li style="margin-bottom: 12px;"><strong>内源性受体降解：</strong>与许多仅起阻断作用的抗体不同，该药能有效诱导细胞表面的[[MET]]受体内吞并进入[[溶酶体]]。这导致了总受体水平的下降，对[[HGF]]依赖型和非依赖型激活均有抑制作用。</li>
        <li style="margin-bottom: 12px;"><strong>抑制旁路激活：</strong>在[[EGFR]]突变的肺癌中，[[MET扩增]]是导致[[TKI]]耐药的主要旁路。[[依米贝妥单抗]]通过清理这些“代偿性”受体，恢复了肿瘤对生长抑制信号的敏感性。</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;">临床研究与应用数据矩阵</h2>

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                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">临床研究领域</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #475569;">联合方案</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">关键数据地位</th>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[NSCLC]] (TKI耐药)</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">联合[[厄洛替尼]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">在[[MET]]高表达亚群中展现出延长[[无进展生存期]]([[PFS]])的潜力。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[转移性胃癌]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">单药及联合[[化疗]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">探索针对[[MET扩增]]型晚期胃癌的后线解救疗效。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[药代动力学]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">多项I期研究</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">证实了其作为大分子抗体在人体内良好的[[半衰期]]与[[安全性]]。</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;">诊疗策略：标志物驱动与联合增效</h2>
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        [[依米贝妥单抗]]的应用强调“[[药检一体]]”的精准管理范式：
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        <li style="margin-bottom: 12px;"><strong>[[MET表达]]精准分层：</strong>由于全人群获益不明显，临床中通过[[IHC]]（[[免疫组化]]）得分（如3+）或[[FISH]]检测[[MET]]/[[CEP7]]比例来筛选高获益人群。</li>
        <li style="margin-bottom: 12px;"><strong>克服耐药联合：</strong>对于[[第三代EGFR-TKI]]耐药且伴有[[MET扩增]]的患者，[[依米贝妥单抗]]联合[[奥希替尼]]等药物是当前重要的探索方向。</li>
        <li style="margin-bottom: 12px;"><strong>[[不良反应]]监控：</strong>主要副作用包含外周[[水肿]]、[[疲劳]]及[[消化道]]反应。由于其属于生物大分子，需警惕偶发的[[输注反应]]。</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>[[MET基因扩增]]：</strong>肿瘤逃逸靶向药物杀伤的重要“救生艇”机制。</li>
            <li style="margin-bottom: 8px;"><strong>[[HGF]]：</strong>肝细胞生长因子，[[MET]]唯一的已知配体，参与组织修复及肿瘤[[转移]]。</li>
            <li style="margin-bottom: 8px;"><strong>[[旁路激活]]：</strong>指肿瘤通过开启另一条信号通路来规避原治疗药物抑制的现象。</li>
            <li style="margin-bottom: 8px;"><strong>[[特泊替尼]]：</strong>同靶点的[[小分子]]抑制剂，常与[[依米贝妥单抗]]进行药效对比。</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>Scagliotti GV, et al. (2020).</strong> <em>Erlotinib with or without emibetuzumab in previously untreated patients with EGFR-mutation-positive NSCLC.</em> <strong>[[Journal of Clinical Oncology]]</strong>.[Academic Review]<br>
            <span style="color: #475569;">[权威点评]：该研究确立了针对MET高表达亚群进行精准分层治疗的必要性，为大分子MET抑制剂的应用指明了方向。</span>
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            [2] <strong>Camidge DR, et al. (2014).</strong> <em>A phase I study of LY2875358 (emibetuzumab), a bivalent MET antibody, in patients with advanced solid tumors.</em> <strong>[[The Lancet Oncology]]</strong>.<br>
            <span style="color: #475569;">[核心价值]：首次在人体中验证了依米贝妥单抗诱导MET降解的生物学效应。</span>
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            [[依米贝妥单抗]] ([[LY2875358]]) 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;">[[MET]]•[[HGF]]•[[EGFR]]•[[AKT]]•[[ERK]]</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;">同类药物</td>
                <td style="padding: 10px 15px; color: #334155;">[[赛沃替尼]]•[[卡马替尼]]•[[奥纳妥珠单抗]]•[[特泊替尼]]</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;">[[礼来]]•[[FDA]]•[[NMPA]]•[[EMA]]</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;">研究前沿</td>
                <td style="padding: 10px 15px; color: #334155;">[[针对MET-ADC药物的续贯研究]]•[[联合免疫检查点抑制剂探索]]•[[液态活检指导下的动态给药]]</td>
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