查看“Trastuzumab”的源代码

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            <strong>曲妥珠单抗</strong>（<strong>Trastuzumab</strong>，研发代号：<strong>huMAb4D5-8</strong>，商品名：<strong>Herceptin/赫赛汀</strong>）是一种重组人源化单克隆抗体，特异性靶向人表皮生长因子受体 2（<strong>[[HER2]]</strong>，又称 <strong>ERBB2</strong>）的胞外结构域 IV。通过阻断 HER2 的同源二聚化、抑制 <strong>[[ADAM17]]</strong> 介导的胞外域脱落以及诱导强效的抗体依赖性细胞毒性（<strong>[[ADCC]]</strong>），曲妥珠单抗显著改善了 HER2 阳性乳腺癌和胃癌患者的预后。在 2026 年的诊疗体系中，曲妥珠单抗不仅作为单一疗法或联合化疗的标准方案，其衍生的双抗及 ADC 药物（如 <strong>[[T-DXd]]</strong>）已将 HER2 靶向治疗带入“低表达（Low）”时代。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">曲妥珠单抗</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Drug: Trastuzumab (点击展开)</div>
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                    <div style="width: 150px; height: 100px; background-color: #f1f5f9; display: flex; align-items: center; justify-content: center; color: #94a3b8; font-size: 0.8em; border-radius: 8px;">Structure: Humanized IgG1-κ</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">HER2 (ERBB2) 靶向单抗</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%;">主要靶点</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #b91c1c;"><strong>HER2 / ERBB2</strong></td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">分子量</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">~148,000 Da</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">CAS 登记号</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">180288-69-1</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">Entrez Gene ID</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">2064</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">UniProt ID</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P04626</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">半衰期</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">约 28.5 天</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">主要风险</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #b91c1c;"><strong>心脏毒性 (LVEF下降)</strong></td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">开发公司</th>
                    <td style="padding: 6px 12px; color: #0f172a;">Genentech (罗氏)</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：四维打击 HER2 阳性细胞</h2>
    
    
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        曲妥珠单抗的抗肿瘤效能不仅源于对生长信号的直接阻断，更涉及免疫系统的精准召集。
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        <li style="margin-bottom: 12px;"><strong>抑制胞外域脱落：</strong>
            <br>曲妥珠单抗结合结构域 IV，阻止金属蛋白酶 <strong>[[ADAM17]]</strong> 剪切 HER2 的胞外部分。这防止了具有高度激酶活性的 <strong>p95HER2</strong> 截短体的形成，该截短体是导致内分泌耐药的关键。</li>
        <li style="margin-bottom: 12px;"><strong>阻断二聚化与信号通路：</strong>
            <br>通过物理空间位阻，曲妥珠单抗干扰 HER2 与其他 HER 家族受体（如 HER3）的配对，抑制下游 <strong>[[PI3K]]/AKT</strong> 及 MAPK 通路的持续激活，诱导细胞周期停滞。</li>
        <li style="margin-bottom: 12px;"><strong>诱导 ADCC 效应：</strong>
            <br>抗体的 Fc 段结合 NK 细胞及巨噬细胞表面的 <strong>[[FcγRIIIA]]</strong>。在 2026 年的转化研究中，通过 <strong>[[Fc 段工程化]]</strong> 增强 ADCC 已成为提升曲妥珠单抗临床响应率的核心方向。</li>
        <li style="margin-bottom: 12px;"><strong>抗血管生成协同：</strong>
            <br>间接下调 <strong>[[VEGF]]</strong> 的表达，通过重塑肿瘤微环境的血管网络来抑制远端转移。</li>
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                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">疾病领域</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">推荐方案 (2026)</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">循证依据/里程碑</th>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">早期乳腺癌</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>TCbH</strong> (曲妥+化疗) 或双靶术后强化。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>HERA 研究</strong>：确立了 1 年辅助治疗的金标准。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">转移性乳腺癌</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">曲妥珠单抗 + <strong>[[帕妥珠单抗]]</strong> + 紫杉类。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>CLEOPATRA 研究</strong>：双靶方案显著延长 OS。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">晚期胃癌</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">曲妥珠单抗 + FP 方案 + <strong>[[PD-1 抑制剂]]</strong>。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>ToGA 研究</strong>：首次确立 HER2 胃癌一线靶向地位。</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;">用药策略：心脏安全与给药管理</h2>
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        <li style="margin-bottom: 12px;"><strong>剂量逻辑：</strong> 初始负荷剂量 8mg/kg，随后每 3 周维持剂量 6mg/kg。2026 年临床趋势更多采用<strong>[[皮下注射 (SC)]]</strong>剂型（含透明质酸酶），给药时间由 90 分钟缩短至 5 分钟。</li>
        <li style="margin-bottom: 12px;"><strong>心脏监测：</strong> 与蒽环类化疗不同，曲妥珠单抗引起的心脏损伤通常是可逆的。要求每 3 个月监测一次 <strong>LVEF</strong>，若下降超过 16% 需暂停用药。</li>
        <li style="margin-bottom: 12px;"><strong>生物类似物应用：</strong> 随着原研药专利到期，全球多个生物类似物（如伊尼妥单抗）已在 2026 年实现广泛替代，显著提升了药物可及性。</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 [Academic Review]</span>
        
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            [1] <strong>Slamon DJ, et al. (2001).</strong> <em>Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2.</em> <strong>[[NEJM]]</strong>. 2001;344(11):783-792.<br>
            <span style="color: #475569;">[点评]：奠基性研究。证明了在化疗中加入曲妥珠单抗可显著提高 HER2 阳性晚期患者的客观缓解率。</span>
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            [2] <strong>Piccart-Gebhart MJ, et al. (2005).</strong> <em>Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer (HERA Trial).</em> <strong>[[NEJM]]</strong>. 2005;353(16):1659-1672.<br>
            <span style="color: #475569;">[点评]：确立了曲妥珠单抗在早期乳腺癌辅助治疗中的 1 年标准疗程地位。</span>
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            [3] <strong>Bang YJ, et al. (2010).</strong> <em>Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric cancer (ToGA).</em> <strong>[[The Lancet]]</strong>.<br>
            <span style="color: #475569;">[点评]：里程碑式突破。将 HER2 靶向治疗从乳腺癌成功扩展至胃肠道恶性肿瘤领域。</span>
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        <h3 style="margin-top: 0; color: #0f172a; font-size: 1.1em;">关键相关概念</h3>
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            [[HER2]] • [[帕妥珠单抗]] • [[T-DXd]] • [[恩美曲妥珠单抗 (T-DM1)]] • [[ADCC]] • [[心脏毒性管理]] • [[HER2-Low]]
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            曲妥珠单抗 (Rituximab) · 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;">[[ERBB2]] • [[HER3]] • [[p95HER2]] • [[FcγRIIIA]]</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;">核心适应症</td>
                <td style="padding: 10px 15px; color: #334155;">[[HER2+ 乳腺癌]] • [[HER2+ 胃癌]] • [[胃食管结合部癌]]</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;">衍生药物</td>
                <td style="padding: 10px 15px; color: #334155;">[[DS-8201]] • [[Margetuximab]] • [[Pyrotinib]] (联用)</td>
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