查看“Tafinlar”的源代码

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            <strong>泰菲乐</strong>（<strong>Tafinlar</strong>，通用名：<strong>达拉非尼/Dabrafenib</strong>）是一种强效、高选择性的口服ATP竞争性<strong>[[BRAF]]</strong>激酶抑制剂。它主要针对携带<strong>[[BRAFV600]]</strong>突变（如V600E、V600K）的肿瘤细胞，通过阻断MAPK信号通路来抑制肿瘤增殖。在2026年的精准肿瘤学实践中，泰菲乐通常与MEK抑制剂<strong>[[曲美替尼]]</strong>联合使用，作为治疗携带BRAF突变的<strong>[[晚期黑色素瘤]]</strong>、<strong>[[非小细胞肺癌]]</strong>及<strong>[[间变性甲状腺癌]]</strong>的标准治疗方案。泰菲乐的出现显著改善了携带特定基因突变患者的生存预后，是实体瘤精准靶向治疗的基石药物之一。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">泰菲乐 (Tafinlar)</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px;">达拉非尼/Dabrafenib · 点击展开详情</div>
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                    <div style="width: 140px; height: 90px; background-color: #f1f5f9; display: flex; align-items: center; justify-content: center; color: #94a3b8; font-size: 0.8em; padding: 10px; text-align: center;">BRAF Inhibitor Structure</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">靶向BRAFV600抑制剂</div>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%;">[[Entrez]]ID</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">673([[BRAF]])</td>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[HGNC]]ID</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">1097</td>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[UniProt]]</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P15056</td>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">分子量</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0;">519.56Da</td>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">给药途径</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">口服(胶囊)</td>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569;">持有公司</th>
                    <td style="padding: 10px 12px;">诺华(Novartis)</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;">作用机制：信号通路级联拦截</h2>
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        泰菲乐的作用核心在于对突变型BRAF激酶活性的特异性干扰，其分子药理过程如下：
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        <li style="margin-bottom: 12px;"><strong>ATP竞争抑制：</strong>泰菲乐能够特异性嵌入BRAFV600激酶结构域的ATP结合位点，阻止磷酸基团转移，使BRAF蛋白失去催化下游<strong>[[MEK]]</strong>蛋白的能力。</li>
        <li style="margin-bottom: 12px;"><strong>高选择性杀伤：</strong>该分子对V600E突变蛋白的抑制效力比野生型高出数百倍，有效降低了对正常细胞信号传导的干扰。</li>
        <li style="margin-bottom: 12px;"><strong>抑制MAPK通路：</strong>通过切断RAS-RAF-MEK-ERK信号级联，诱导肿瘤细胞发生G1期细胞周期停滞并启动凋亡程序。</li>
        <li style="margin-bottom: 12px;"><strong>联合拦截策略：</strong>与曲美替尼联用可实现对MAPK通路的“双重打击”，防止旁路激活并显著延缓<strong>[[获得性耐药]]</strong>的发生。</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;">核心临床研究矩阵</h2>
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                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">研究项目</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">适应症/方案</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">关键客观数据</th>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[BREAK-3]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">晚期黑色素瘤(单药对照)</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">相比传统化疗，显著延长PFS(5.1 vs 2.7个月)且缓解率更高。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[COMBI-d/v]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">泰菲乐+迈吉宁(双靶联合)</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">5年OS率达34%，确立了BRAFV600突变黑色素瘤的标准疗法。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[ROAR]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">间变性甲状腺癌/胆管癌</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">在难治性ATC患者中ORR达到64%，开启了罕见瘤种精准治疗新篇章。</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：不良反应与精准管理</h2>
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        <li style="margin-bottom: 12px;"><strong>发热反应监控：</strong>发热是泰菲乐最常见的特征性副作用。2026年共识建议：体温超过38.5℃应暂停给药并辅以物理降温或对症治疗，热退后再恢复原剂量。</li>
        <li style="margin-bottom: 12px;"><strong>皮肤病变评估：</strong>需警惕新发皮肤原发肿瘤（如<strong>[[鳞状细胞癌]]</strong>）。联合曲美替尼可显著降低此类风险，但仍需定期进行专业皮肤科检查。</li>
        <li style="margin-bottom: 12px;"><strong>视力与心脏监测：</strong>由于对信号通路的抑制，少数患者可能出现葡萄膜炎或LVEF下降，需定期随访相关指标。</li>
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        <h3 style="margin-top: 0; color: #0f172a; font-size: 1.15em; margin-bottom: 20px; border-bottom: 2px solid #3b82f6; display: inline-block; padding-bottom: 5px;">关键相关概念</h3>
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            <div style="color: #334155;"><strong style="color: #1e40af;">[[BRAFV600E]]</strong>：泰菲乐起效的核心生物标志物，广泛存在于黑色素瘤及多种实体瘤中。</div>
            <div style="color: #334155;"><strong style="color: #1e40af;">[[曲美替尼]]</strong>：商品名迈吉宁，泰菲乐的“最佳拍档”，用于抑制MEK蛋白以增强疗效。</div>
            <div style="color: #334155;"><strong style="color: #1e40af;">[[MAPK通路]]</strong>：肿瘤细胞生长增殖的关键信号通路，是达拉非尼作用的生化战场。</div>
            <div style="color: #334155;"><strong style="color: #1e40af;">[[维罗非尼]]</strong>：首个获批的BRAF抑制剂，常作为泰菲乐临床应用的同类参照。</div>
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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>
        
        <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;">
            [1] <strong>Hauschild A, et al. (2012).</strong> <em>Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial (BREAK-3).</em> <strong>[[The Lancet]]</strong>. 2012;380(9839):358-365.<br>
            <span style="color: #475569;">[学术点评]：基石研究。确立了达拉非尼单药在BRAF突变黑色素瘤二线及一线治疗中的卓越地位。</span>
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            [2] <strong>Robert C, et al. (2015).</strong> <em>Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib.</em> <strong>[[NEJM]]</strong>. 2015;372(1):30-39.<br>
            <span style="color: #475569;">[学术点评]：联合治疗范式。该研究证明了双靶联合在延长总生存期方面的里程碑意义。</span>
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            [3] <strong>Subbiah V, et al. (2020).</strong> <em>Dabrafenib and Trametinib Treatment in Patients With BRAF V600E–Mutant Biliary Tract Cancer (ROAR).</em> <strong>[[The Lancet Oncology]]</strong>. 2020;21(11):1496-1505.<br>
            <span style="color: #475569;">[前沿指南]：泛癌种探索。证实了泰菲乐组合在胆管癌等难治性实体瘤中的广谱精准打击能力。</span>
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            泰菲乐 (Tafinlar / Dabrafenib) · 知识图谱导航
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                <td style="width: 100px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 15px; text-align: left; vertical-align: middle;">核心基因</td>
                <td style="padding: 10px 15px; color: #334155; text-align: left;">[[BRAF]] • [[MEK1]] • [[MAPK1]] • [[RAS]] • [[ERK]]</td>
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                <td style="width: 100px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 15px; text-align: left; vertical-align: middle;">目标疾病</td>
                <td style="padding: 10px 15px; color: #334155; text-align: left;">[[黑色素瘤]] • [[非小细胞肺癌]] • [[间变性甲状腺癌]] • [[胆管癌]]</td>
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                <td style="width: 100px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 15px; text-align: left; vertical-align: middle;">生化过程</td>
                <td style="padding: 10px 15px; color: #334155; text-align: left;">[[激酶抑制]] • [[细胞周期停滞]] • [[双靶向协同]] • [[耐药机制研究]]</td>
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                <td style="width: 100px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 15px; text-align: left; vertical-align: middle;">临床协同</td>
                <td style="padding: 10px 15px; color: #334155; text-align: left;">[[曲美替尼]] • [[帕博利珠单抗]] • [[基因检测]] • [[发热管理]]</td>
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