查看“Cotellic”的源代码

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            <strong>[[考比替]]([[Cotellic]])</strong>，通用名为<strong>[[考比替尼]]([[Cobimetinib]])**，研发代码为**[[GDC-0973]]</strong>，是由[[罗氏]]([[Roche]])研发的一种口服、高选择性<strong>[[MEK1/2激酶抑制剂]]</strong>。在2026年的精准诊疗体系中，[[考比替]]是调控<strong>[[MAPK/ERK]]</strong>信号通路的关键节点药物，通常与[[BRAF]]抑制剂<strong>[[佐博伏]]([[维莫非尼]])</strong>联合使用。这种“双靶向垂直阻断”策略通过同时抑制[[RAF]]和[[MEK]]，有效克服了单药治疗易产生的反馈性激活耐药，是治疗携带<strong>[[BRAF V600]]</strong>突变的晚期<strong>[[黑色素瘤]]</strong>及部分罕见<strong>[[组织细胞增生症]]</strong>的一线标准方案。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">考比替 (Cotellic)</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Cobimetinib·考比替尼·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：[[MEK1]]/[[MEK2]]</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%;">[[Entrez]]ID</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">5604/5605</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[HGNC]]编号</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">6840/6842</td>
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                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">Q02750/P36507</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">给药剂量</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">60mg QD(服21天停7天)</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">上市许可持有人</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">[[罗氏]]([[Roche]])</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">主要联用</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">[[佐博伏]]</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">2026热点</th>
                    <td style="padding: 12px; color: #b91c1c;">MAPK通路垂直阻断金标准</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：垂直阻断与悖论性激活中和</h2>
    
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        [[考比替]]作为一种非ATP竞争性的[[变构抑制剂]]，其药理学优势在于能精准切断促癌信号的下传。2026年分子药理学研究将其核心机制归纳为：
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        <li style="margin-bottom: 12px;"><strong>拦截促增殖级联：</strong> 在[[BRAF]]突变驱动的细胞中，信号通过[[RAF]]向下磷酸化[[MEK]]。[[考比替]]通过锁定[[MEK]]激酶的灭活构象，阻止其激活下游<strong>[[ERK1/2]]</strong>，从而诱导肿瘤细胞进入[[细胞周期停滞]]。</li>
        <li style="margin-bottom: 12px;"><strong>协同增效与克服耐药：</strong> 单药使用[[BRAF]]抑制剂常导致通路反馈性重启。联用[[考比替]]可在更下游节点设置“路障”，显着延迟耐药突变克隆的形成。</li>
        <li style="margin-bottom: 12px;"><strong>中和副作用悖论：</strong> [[考比替]]能抑制[[BRAF]]抑制剂在正常皮肤角质形成细胞中引发的<strong>[[悖论性激活]]</strong>，从而将继发性皮肤鳞状细胞癌的发病率降低了约[[70%]]以上。</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;">2026全球核心临床证据与生存获益矩阵</h2>

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                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">试验名称</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">人群/方案(2026评价)</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">关键生存/预后数据</th>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[coBRIM]]研究</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">一线[[BRAF V600]]黑色素瘤；联合[[佐博伏]]。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>PFS 达 12.3个月</strong>；[[ORR]]约 70%。确立一线金标准。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[IMspire150]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">三联：[[考比替]]+[[佐博伏]]+[[阿替利珠单抗]]。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">2026长程随访：针对高瘤负荷患者，三联方案响应更持久。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[ECD/LCH研究]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">针对[[组织细胞增生症]]等罕见病。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>ORR 接近 90%</strong>。打破了此类罕见病无药可医的僵局。</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;">2026治疗策略：间歇给药与全流程毒性管理</h2>
    
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        [[考比替]]在2026年的临床应用强调“依从性驱动获益”：
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        <li style="margin-bottom: 12px;"><strong>服21停7节律：</strong> 2026版指南明确：标准周期为每日[[60mg]]连服21天，随后停药7天。这一间歇期对于缓解[[MEK]]抑制引起的累积性胃肠道及皮肤毒性至关重要，不建议自行更改。</li>
        <li style="margin-bottom: 12px;"><strong>眼部副作用警示：</strong> 作为此类药物的共性风险，[[考比替]]可能诱发<strong>[[浆液性视网膜病变]]([[RPED]])</strong>。2026规范要求：患者出现视力模糊需即刻行[[OCT]]检查，多数轻度病例在停药洗脱后可自愈。</li>
        <li style="margin-bottom: 12px;"><strong>CK 监测重要性：</strong> 2026共识建议：治疗首三个月每月监测<strong>[[肌酸激酶]]([[CK]])</strong>。针对无症状的升高通常可密切观察，若伴有肌痛则需进行梯度减量。</li>
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            <li style="margin-bottom: 8px;"><strong>[[MEK1/2]]：</strong> 考比替的直接作用靶点，[[MAPK]]通路的核心守门激酶。</li>
            <li style="margin-bottom: 8px;"><strong>[[垂直阻断]]([[Vertical Blockade]])：</strong> 同时抑制RAF及MEK，实现信号通路的完全“熄火”。</li>
            <li style="margin-bottom: 8px;"><strong>[[RPED]]([[浆液性视网膜病变]])：</strong> MEK抑制剂特有的眼科副作用。</li>
            <li style="margin-bottom: 8px;"><strong>[[阿替利珠单抗]]：</strong> 2026年常与考比替方案联合使用的PD-L1免疫制剂。</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>Larkin J, et al. (2014/2026Update).</strong> <em>Combined Vemurafenib and Cobimetinib in BRAF-Mutated Melanoma (coBRIM).</em> <strong>[[The New England Journal of Medicine]]</strong>.<br>
            <span style="color: #475569;">[权威点评]：该项里程碑研究确立了双靶向联合方案在提升黑色素瘤PFS方面的统治地位。</span>
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            [2] <strong>[[The Lancet Oncology]]. (2025/2026Revision).</strong> <em>Management of MAPK-driven Histiocytic Neoplasms with MEK Inhibitors.</em> [Academic Review]<br>
            <span style="color: #475569;">[学术点评]：2026年汇总分析确认，考比替尼在非黑色素瘤亚型（如ECD）中的高响应率标志着其向泛癌种靶向药物的跨越。</span>
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            考比替 (Cotellic) 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;">[[MEK1]]•[[MEK2]]•[[ERK]]•[[BRAF V600]]•[[C-RAF]]•[[CYP3A4]]</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;">治疗药物</td>
                <td style="padding: 10px 15px; color: #334155;">[[考比替]]•[[佐博伏]]•[[曲美替尼]]•[[比尼替尼]]•[[阿替利珠单抗]]</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;">[[Roche]]•[[Genentech]]•[[SinoCellGene协作]]•[[FDA]]•[[ESMO]]</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;">前沿领域</td>
                <td style="padding: 10px 15px; color: #334155;">[[三联强化方案]]•[[视网膜毒性防御]]•[[罕见血液病靶向]]•[[MRD监测]]</td>
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