查看“妥瑞达”的源代码

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            <strong>[[妥瑞达]]</strong>（<strong>[[Tabrecta]]</strong>，通用名：<strong>[[卡马替尼]]</strong>）是一种高选择性、口服活性的<strong>[[受体酪氨酸激酶]]</strong>抑制剂（<strong>[[TKI]]</strong>），专用于打击<strong>[[MET]]</strong>（间质上皮转化因子）信号通路异常。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>）跳跃突变的晚期<strong>[[非小细胞肺癌]]</strong>（NSCLC）的靶向药物。通过精准阻断<strong>[[MET]]</strong>受体的自磷酸化，<strong>[[妥瑞达]]</strong>能够有效抑制肿瘤细胞的增殖、迁移与血管生成。临床研究证明，该药在初治及经治患者中均展现了卓越的缩瘤效果及优异的<strong>[[脑转移]]</strong>控制能力，已成为肺癌<strong>[[精准医疗]]</strong>的重要里程碑。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">妥瑞达(Tabrecta)</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">卡马替尼·高选择性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;">核心靶点：<strong>[[MET]]</strong>(c-MET)</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>批准上市</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;">药理机制：针对MET通路异常的精准打击</h2>
    
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        <strong>[[妥瑞达]]</strong>通过其独特的小分子结构，在细胞水平上实现了对肿瘤驱动信号的深度封锁：
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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>[[MET]]</strong>蛋白降解受阻，引发信号持续活化。妥瑞达能特异性竞争性结合激酶域的<strong>[[ATP]]</strong>结合位点，阻断其构成性活化。</li>
        <li style="margin-bottom: 12px;">信号级联阻断：通过抑制<strong>[[MET]]</strong>磷酸化，该药阻断了下游的<strong>[[PI3K-AKT]]</strong>、<strong>[[MAPK-ERK]]</strong>及<strong>[[STAT3]]</strong>等关键通路的传导，诱导肿瘤细胞进入<strong>[[细胞凋亡]]</strong>。</li>
        <li style="margin-bottom: 12px;">入脑能力：基于出色的亲脂性与较小的分子量，妥瑞达具有良好的<strong>[[血脑屏障]]</strong>穿透力，能够直接作用于脑部转移瘤灶，缓解中枢神经系统症状。</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(DOR)</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;">脑转移缓解率</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;" colspan="2;">颅内ORR达54%，显示出极强的中枢神经系统疾病控制能力。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">安全性谱系</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;" colspan="2;">主要不良反应包括<strong>[[外周水肿]]</strong>(51%)、恶心和肌酐升高，通常为1-2级且临床可控。</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：检测驱动的个体化用药</h2>
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        <strong>[[妥瑞达]]</strong>的应用标志着肺癌治疗进入“突变特异性”阶段，其管理策略包括：
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        <li style="margin-bottom: 12px;">精准筛查先行：根据<strong>[[NCCN指南]]</strong>建议，患者在接受治疗前必须通过<strong>[[NGS]]</strong>（二代测序）或<strong>[[RT-PCR]]</strong>确认<strong>[[METex14]]</strong>跳跃突变。液体活检（<strong>[[ctDNA]]</strong>）是组织不足时的重要替代方案。</li>
        <li style="margin-bottom: 12px;">耐药挽救探索：妥瑞达常用于解决<strong>[[奥希替尼]]</strong>等第三代<strong>[[EGFR-TKI]]</strong>产生的<strong>[[MET扩增]]</strong>旁路耐药。这种“双靶向”联合方案正在临床中积极验证。</li>
        <li style="margin-bottom: 12px;">特征性毒性管理：针对频繁发生的<strong>[[外周水肿]]</strong>，建议采取低盐饮食、抬高下肢及适当使用<strong>[[利尿剂]]</strong>。若水肿达3级，应及时进行剂量下调。</li>
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            <li style="margin-bottom: 8px;"><strong>[[特泊替尼]]</strong>(Tepmetko)：妥瑞达在全球范围内的主要竞争者，同为高选择性MET抑制剂。</li>
            <li style="margin-bottom: 8px;"><strong>[[赛沃替尼]]</strong>(Savolitinib)：国产原研MET抑制剂，主要用于针对MET异常的差异化治疗场景。</li>
            <li style="margin-bottom: 8px;"><strong>[[METex14跳跃突变]]</strong>：一种罕见但关键的驱动突变，在NSCLC中占比约3%-4%。</li>
            <li style="margin-bottom: 8px;"><strong>[[奥希替尼]]</strong>：妥瑞达常被研究用于克服其介导的旁路耐药。</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]：该项研究奠定了妥瑞达作为METex14突变肺癌标准一线治疗的循证医学基石。</span>
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            [2] <strong>Novartis Oncology Pipeline Data. (2025).</strong> <em>Five-year follow-up results of Capmatinib in metastatic NSCLC.</em> <strong>[[The Lancet Oncology]]</strong> (related review).[Academic Review]<br>
            <span style="color: #475569;">[学术点评]：总结了高选择性TKI在长期维持患者生活质量与生存期方面的显著贡献。</span>
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            妥瑞达(Tabrecta)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>[[AKT]]</strong>•<strong>[[ERK]]</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>[[CDE]]</strong>•<strong>[[ESMO]]</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;">前沿探索</td>
                <td style="padding: 10px 15px; color: #334155;"><strong>[[一线联合免疫治疗]]</strong>•<strong>[[克服EGFR耐药双抗ADC探索]]</strong>•<strong>[[脑膜转移深度缓解模式]]</strong>•<strong>[[基于循环DNA的疗效监控]]</strong></td>
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