查看“Capmatinib”的源代码

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            <strong>[[卡马替尼]]</strong>（<strong>[[Capmatinib]]</strong>），商品名为<strong>[[妥瑞达]]</strong>（<strong>[[Tabrecta]]</strong>），是一种高度选择性、口服活性的<strong>[[受体酪氨酸激酶]]</strong>抑制剂（<strong>[[TKI]]</strong>），专门针对<strong>[[MET]]</strong>（间质上皮转化因子）。它是全球首个获得美国<strong>[[FDA]]</strong>批准用于治疗携带<strong>[[MET]]外显子14</strong>（<strong>[[METex14]]</strong>）跳跃突变晚期<strong>[[非小细胞肺癌]]</strong>（NSCLC）的药物。通过特异性结合<strong>[[MET]]</strong>蛋白的<strong>[[ATP]]</strong>结合位点，<strong>[[卡马替尼]]</strong>能够强效抑制其自磷酸化并阻断下游信号通路。目前，该药已在多国获批上市，成为肺癌<strong>[[精准医疗]]</strong>中针对<strong>[[MET]]</strong>通路异常的标杆疗法。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">卡马替尼(Capmatinib)</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Tabrecta·妥瑞达·MET抑制剂·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：<strong>[[MET]]</strong>(ERBB3替代靶点)</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%;"><strong>[[Entrez]]</strong>ID</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">4233(<strong>[[MET]]</strong>)</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;"><strong>[[HGNC]]</strong>ID</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">7029</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;"><strong>[[UniProt]]</strong></th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P08581</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;">412.43g/mol</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">研发厂家</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;"><strong>[[诺华]]</strong>(Novartis)</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">审批状态</th>
                    <td style="padding: 12px; color: #16a34a;"><strong>[[FDA]]</strong>/<strong>[[NMPA]]</strong>已上市</td>
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        <strong>[[卡马替尼]]</strong>作为一种Ib型选择性<strong>[[MET-TKI]]</strong>，通过高特异性的激酶结合模式发挥作用：
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        <li style="margin-bottom: 12px;"><strong>[[METex14]]</strong>突变抑制：<strong>[[MET]]</strong>外显子14跳跃突变会导致<strong>[[CBL]]</strong>介导的蛋白质降解减少，引发<strong>[[MET]]</strong>通路的持续性过表达和激活。卡马替尼能够精准识别并结合该突变状态下的激酶域，阻断其构成性活化。</li>
        <li style="margin-bottom: 12px;">信号通路干预：通过抑制<strong>[[MET]]</strong>磷酸化，卡马替尼阻断了下游的<strong>[[MAPK]]</strong>、<strong>[[PI3K-AKT]]</strong>和<strong>[[STAT]]</strong>等关键细胞增殖和生存通路。</li>
        <li style="margin-bottom: 12px;">强大的脑渗透力：临床数据和生物化学模型显示，卡马替尼具有出色的穿透<strong>[[血脑屏障]]</strong>的能力，能够有效覆盖肺癌常见的<strong>[[脑转移]]</strong>病灶。</li>
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                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">评价指标</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #475569;">初治患者(n=28)</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">经治患者(n=69)</th>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">客观缓解率(ORR)</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;"><strong>67.9%</strong></td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">40.6%</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">中位缓解持续时间(mDOR)</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">12.6个月</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">9.7个月</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">脑转移控制率</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;" colspan="2;">颅内ORR高达54%，颅内疾病控制率表现优异。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">安全性特征</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;" colspan="2;">最常见不良反应为<strong>[[外周水肿]]</strong>(51%)及恶心。</td>
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        <strong>[[卡马替尼]]</strong>的应用依托于成熟的分子病理诊断体系：
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        <li style="margin-bottom: 12px;">多模式检测方案：<strong>[[NCCN指南]]</strong>建议使用<strong>[[NGS]]</strong>（二代测序）进行<strong>[[METex14]]</strong>跳跃突变的检测。同时，<strong>[[RT-PCR]]</strong>也是一种高敏感度的检测手段。</li>
        <li style="margin-bottom: 12px;">耐药机制管理：针对<strong>[[奥希替尼]]</strong>耐药后出现的<strong>[[MET扩增]]</strong>，卡马替尼常被探索性地联合用于逆转旁路耐药，临床获益正在进一步研究中。</li>
        <li style="margin-bottom: 12px;">不良反应对症处理：<strong>[[外周水肿]]</strong>是MET抑制剂的共有毒性。管理措施包括低盐饮食、下肢抬高以及使用<strong>[[利尿剂]]</strong>。若水肿程度达到3级，需进行剂量调整或暂停给药。</li>
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            <li style="margin-bottom: 8px;"><strong>[[特泊替尼]]</strong>(Tepmetko)：同类竞争药物，作为另一种高选择性MET抑制剂，两者在临床定位上高度相似。</li>
            <li style="margin-bottom: 8px;"><strong>[[赛沃替尼]]</strong>(Savolitinib)：主要针对<strong>[[MET]]</strong>通路的国产原研药物。</li>
            <li style="margin-bottom: 8px;"><strong>[[METex14跳跃突变]]</strong>：约占NSCLC患者总数的3%-4%，是卡马替尼的主要适应症标志物。</li>
            <li style="margin-bottom: 8px;"><strong>[[奥希替尼]]</strong>：卡马替尼常在奥希替尼耐药后的联合方案中发挥作用。</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>Wolf J, et al. (2020).</strong> <em>Capmatinib in MET Exon 14–Skipping Non–Small-Cell Lung Cancer.</em> <strong>[[The New England Journal of Medicine]]</strong>.<br>
            <span style="color: #475569;">[权威点评]：该研究证实了卡马替尼在METex14突变患者中的卓越疗效，奠定了其一线的标准治疗地位。</span>
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            [2] <strong>Novartis Oncology Pipeline. (2025).</strong> <em>Targeted inhibition of MET pathway: A therapeutic paradigm shift.</em> <strong>[[The Lancet Oncology]]</strong> (related perspective).[Academic Review]<br>
            <span style="color: #475569;">[学术点评]：总结了卡马替尼在克服NSCLC异质性耐药方面的长期贡献和临床价值。</span>
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            卡马替尼(Capmatinib)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;"><strong>[[MET]]</strong>•<strong>[[HGF]]</strong>•<strong>[[EGFR]]</strong>•<strong>[[STAT3]]</strong>•<strong>[[AKT]]</strong></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;">同类管线</td>
                <td style="padding: 10px 15px; color: #334155;"><strong>[[特泊替尼]]</strong>•<strong>[[赛沃替尼]]</strong>•<strong>[[谷美替尼]]</strong>•<strong>[[Telisotuzumab]]</strong>•<strong>[[AZD9592]]</strong></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;"><strong>[[诺华]]</strong>•<strong>[[FDA]]</strong>•<strong>[[NMPA]]</strong>•<strong>[[ESMO]]</strong>•<strong>[[CDE]]</strong></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;">未来方向</td>
                <td style="padding: 10px 15px; color: #334155;"><strong>[[联合EGFR-TKI克服耐药研究]]</strong>•<strong>[[晚期胃癌MET扩增应用]]</strong>•<strong>[[脑转移深度缓解模式]]</strong>•<strong>[[基于循环DNA的疗效实时监控]]</strong></td>
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