查看“恩诺单抗”的源代码

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            <strong>[[恩诺单抗]]</strong>（<strong>[[Enfortumab Vedotin]]</strong>）是一种创新的、针对<strong>[[Nectin-4]]</strong>蛋白的<strong>[[抗体偶联药物]]</strong>（<strong>[[ADC]]</strong>）。该药物由[[Seagen]]（现[[辉瑞]]）与[[安斯泰来]]联合开发，专门用于治疗<strong>[[尿路上皮癌]]</strong>（[[UC]]）。[[恩诺单抗]]由靶向[[Nectin-4]]的人源化[[单克隆抗体]]通过[[蛋白酶]]可切割[[链接子]]与强效[[微管抑制剂]]<strong>[[MMAE]]</strong>（[[一甲基澳瑞他汀E]]）偶联而成。在当前的[[精准肿瘤学]]临床实践中，[[恩诺单抗]]联合<strong>[[帕博利珠单抗]]</strong>（[[PD-1抑制剂]]）已确立为晚期[[膀胱癌]]一线治疗的金标准，显著延长了患者的[[总生存期]]。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">[[恩诺单抗]]</div>
            <div style="font-size: 0.75em; opacity: 0.85; margin-top: 4px;">[[Enfortumab Vedotin]] · [[ADC]] · 点击展开</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心靶标：[[Nectin-4]]</div>
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                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">81607([[PVRL4]])</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;">19668</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;">Q96NY8</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">载药([[Payload]])</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #b91c1c;">[[MMAE]]</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152kDa</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569;">开发实体</th>
                    <td style="padding: 12px; color: #0f172a;">[[辉瑞]] / [[安斯泰来]]</td>
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        [[恩诺单抗]]的治疗效应源于其对[[尿路上皮癌]]高度特异性表达的[[Nectin-4]]（[[细胞黏附分子]]）的精准识别：
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        <li style="margin-bottom: 12px;"><strong>靶向结合与[[内吞]]：</strong>[[恩诺单抗]]与肿瘤细胞表面的[[Nectin-4]]高亲和力结合后，通过[[受体介导的内吞作用]]进入细胞内部。</li>
        <li style="margin-bottom: 12px;"><strong>[[溶酶体]]降解与释放：</strong>进入细胞后，偶联物被转运至[[溶酶体]]，其[[缬氨酸-瓜氨酸]]链接子被胞内[[蛋白酶]]裂解，释放活性载药<strong>[[MMAE]]</strong>。</li>
        <li style="margin-bottom: 12px;"><strong>微管破坏与[[凋亡]]：</strong>自由的[[MMAE]]结合细胞内的[[微管蛋白]]，破坏[[有丝分裂]]中的[[纺锤体]]形成，将细胞周期锁定在[[G2/M期]]，最终诱导细胞发生[[程序性凋亡]]。</li>
        <li style="margin-bottom: 12px;"><strong>[[旁观者效应]]：</strong>释放的[[MMAE]]具有膜通透性，可扩散至邻近不表达[[Nectin-4]]的肿瘤细胞，进一步扩大杀伤范围。</li>
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                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">试验代号</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #475569;">研究人群/分期</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">当前地位与关键数据</th>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[EV-302]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">晚期[[UC]]一线治疗</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">联合[[帕博利珠单抗]]，较传统化疗降低死亡风险约53%，成为全球一线金标准。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[EV-301]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">经治[[UC]]后线治疗</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">证实[[恩诺单抗]]单药在[[化疗]]和[[免疫治疗]]进展后的生存获益。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[EV-202]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">多种[[实性肿瘤]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">探索针对[[胸腺癌]]、[[头颈鳞癌]]等[[Nectin-4]]阳性肿瘤的疗效。</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：精准应用与毒性预警</h2>
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        [[恩诺单抗]]的应用彻底改变了晚期[[尿路上皮癌]]的诊疗路径，但其毒性管理仍是临床重点：
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        <li style="margin-bottom: 12px;"><strong>[[皮肤毒性]]管理：</strong>由于皮肤基底层亦表达[[Nectin-4]]，患者常出现[[皮疹]]、[[瘙痒]]，严重者可发生[[SJS]]/[[TEN]]。治疗期间应密切监测并早期应用[[皮质激素]]。</li>
        <li style="margin-bottom: 12px;"><strong>[[周围神经病变]]：</strong>[[MMAE]]载荷可引起感觉或运动神经损伤。需定期评估患者肢端麻木感，必要时采取[[减量]]或[[暂停用药]]策略。</li>
        <li style="margin-bottom: 12px;"><strong>[[高血糖]]风险：</strong>[[恩诺单抗]]可诱发严重的甚至致命的[[高血糖]]。在给药前及给药期间需常规监测[[血糖]]水平，糖尿病患者需严密观察。</li>
        <li style="margin-bottom: 12px;"><strong>联合[[PD-1]]的序贯性：</strong>目前首选联合方案。对于不耐受[[顺铂]]的一线患者，该联合方案已成为最优选择。</li>
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            <li style="margin-bottom: 8px;"><strong>[[Nectin-4]]：</strong>属于[[细胞黏附分子]]家族，在[[膀胱癌]]、[[乳腺癌]]等上皮肿瘤中高表达，是极佳的ADC靶标。</li>
            <li style="margin-bottom: 8px;"><strong>[[MMAE]]：</strong>一种合成的抗微管药，因毒性极强无法直接全身给药，需通过ADC形式精准释放。</li>
            <li style="margin-bottom: 8px;"><strong>[[尿路上皮癌]]：</strong>最常见的[[膀胱癌]]病理类型，对[[恩诺单抗]]具有高度敏感性。</li>
            <li style="margin-bottom: 8px;"><strong>[[旁观者效应]]：</strong>ADC载药跨细胞膜扩散杀伤非靶向细胞的能力。</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>Powles T, et al. (2024).</strong> <em>Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer (EV-302).</em> <strong>[[The New England Journal of Medicine]]</strong>.[Academic Review]<br>
            <span style="color: #475569;">[权威点评]：EV-302研究彻底终结了化疗在晚期膀胱癌一线的统治地位，将总生存期翻倍。</span>
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        <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;">
            [2] <strong>Astellas Pharma Inc. (2025).</strong> <em>Clinical Efficacy and Safety Profile of Padcev in Global Populations.</em> <strong>[[The Lancet Oncology]]</strong>.<br>
            <span style="color: #475569;">[核心价值]：对恩诺单抗在全球真实世界中的安全性，特别是针对亚洲人群的皮肤毒性管理提供了详实证据。</span>
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            [[恩诺单抗]] ([[Padcev]]) 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;">[[Nectin-4]]•[[微管蛋白]]•[[PD-1]]•[[HER2]]</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;">适应症</td>
                <td style="padding: 10px 15px; color: #334155;">[[晚期尿路上皮癌]]•[[膀胱癌]]•[[经治乳腺癌]]•[[头颈鳞癌]]</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;">[[辉瑞]]•[[安斯泰来]]•[[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;">[[新辅助联合PD-1治疗肌肉浸润性膀胱癌]]•[[针对HER2耐药患者的ADC续贯]]•[[皮肤毒性预判生物标志物]]</td>
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