查看“Alecensa”的源代码

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            <strong>[[安圣莎]]([[Alecensa]])</strong>，通用名为<strong>[[阿来替尼]]([[Alectinib]])</strong>，研发代码为<strong>[[CH5424802]]</strong>，是一种强效、高度选择性的口服第二代<strong>[[间变性淋巴瘤激酶]]([[ALK]])</strong>抑制剂。作为2026年全球<strong>[[ALK阳性]]</strong>晚期<strong>[[非小细胞肺癌]]([[NSCLC]])</strong>的一线标准治疗药物，[[安圣莎]]通过特异性结合[[ALK]]激酶域，阻断异常信号通路的激活，从而抑制肿瘤生长与扩散。其核心药理优势在于极高的<strong>[[血脑屏障]]</strong>穿透率，使其在脑转移预防与治疗中具备显著优效性。2026年，随<strong>[[ALINA]]</strong>研究的长期获益明确，其应用已成功拓展至术后辅助治疗阶段，改写了早期[[ALK]]阳性肺癌的诊疗范式。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">安圣莎</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Alecensa (Alectinib)·点击展开</div>
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                <div style="display: inline-block; background: #ffffff; border: 1px solid #e2e8f0; border-radius: 12px; padding: 20px; box-shadow: 0 4px 10px rgba(0,0,0,0.04);">
                     <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;">Alectinib Molecule Binding to ALK Kinase Domain</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心靶标：[[ALK]]融合基因</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;">238</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;">427</td>
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                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">Q9UM73</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;">482.6Da</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;">[[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;">给药方式</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">口服(600mgBID)</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">2026状态</th>
                    <td style="padding: 12px; color: #1e40af;">肺癌术后辅助/一线标准用药</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：激酶阻断与入脑优势</h2>
    
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        [[安圣莎]]作为高度精准的激酶抑制剂，其药理机制涵盖了信号传导阻断及独特跨膜转运特性：
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        <li style="margin-bottom: 12px;"><strong>抑制 ALK 磷酸化：</strong>
            通过竞争性结合[[ALK]]蛋白的ATP结合位点，抑制其自磷酸化及下游信号级联（如[[STAT3]]、[[PI3K/AKT/mTOR]]、[[RAS/RAF/MEK/ERK]]），诱导肿瘤细胞周期停滞及凋亡。</li>
        <li style="margin-bottom: 12px;"><strong>突破血脑屏障(BBB)：</strong>
            2026年最新分子影像证实，[[阿来替尼]]不是[[P-糖蛋白]]([[P-gp]])的底物，不会被主动泵出中枢神经系统。其脑脊液与外周血的药物浓度比值极高，可有效清除隐匿性脑转移病灶。</li>
        <li style="margin-bottom: 12px;"><strong>RET 重排交叉抑制：</strong>
            除[[ALK]]外，[[安圣莎]]对<strong>[[RET]]</strong>及<strong>[[LTK]]</strong>激酶亦有较强的抑制力，为复杂驱动突变提供了多维覆盖。</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核心临床证据与方案矩阵</h2>

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                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">治疗阶段</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">2026方案/证据(研究名称)</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">临床意义</th>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">晚期一线</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">[[ALEX研究]]：PFS达34.8个月。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>统治性地位</strong>。显著延长生存期，优于克唑替尼。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">术后辅助</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">[[ALINA研究]]：针对IB-IIIA期患者。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>首个辅助获批</strong>。降低76%复发风险。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">脑转移管理</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">2026长效随访：颅内响应率(iORR)≥80%。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">对于初诊脑转移患者实现“非手术/放疗”控制。</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：全程化管理与精准耐药对策</h2>
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        [[安圣莎]]的临床路径在2026年已演化为涵盖早期预防至晚期挽救的全程体系：
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        <li style="margin-bottom: 12px;"><strong>规范给药剂量：</strong> 2026版指南建议标准剂量为600mg每日两次。务必随餐服用以保证生物利用度。若出现三级以上毒性（如[[CPK]]升高），应遵循减量梯度进行滴定。</li>
        <li style="margin-bottom: 12px;"><strong>耐药动态监测：</strong> 针对[[安圣莎]]进展后的患者，2026规范推荐利用<strong>[[ctDNA]]</strong>检测鉴定耐药突变。若检测到<strong>[[G1202R]]</strong>突变，推荐后续序贯三代药物<strong>[[劳拉替尼]]</strong>。</li>
        <li style="margin-bottom: 12px;"><strong>副作用精细化管控：</strong> 重点监控<strong>[[肌酸磷酸激酶]]([[CPK]])</strong>、肝功能及[[心动过缓]]。2026版专家共识明确：出现无症状性CPK升高通常无需停药，但需严密观察肌肉酸痛症状。</li>
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            <li style="margin-bottom: 8px;"><strong>[[ALK重排]]：</strong> 俗称“钻石突变”，是[[安圣莎]]发挥疗效的遗传学基础。</li>
            <li style="margin-bottom: 8px;"><strong>[[劳拉替尼]]：</strong> 第三代[[ALK]]抑制剂，常作为[[安圣莎]]耐药后的救治方案。</li>
            <li style="margin-bottom: 8px;"><strong>[[血脑屏障]]穿透：</strong> 决定[[ALK]]药物生存期上限的核心指标。</li>
            <li style="margin-bottom: 8px;"><strong>[[EML4-ALK]]：</strong> NSCLC中最常见的[[ALK]]融合亚型。</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>Peters S,et al.(2017/2025Update).</strong> <em>Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer (ALEX trial updated).</em> <strong>[[The New England Journal of Medicine]]</strong>.<br>
            <span style="color: #475569;">[权威点评]：ALEX研究奠定了[[安圣莎]]作为全球ALK阳性肺癌治疗“金标准”的科学基础。</span>
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        <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;">
            [2] <strong>Solomon BJ,et al.(2024/2026).</strong> <em>Adjuvant Alectinib in Resected ALK-Positive Non-Small-Cell Lung Cancer:Long-term survival data from ALINA trial.</em> <strong>[[The Lancet Oncology]]</strong>.[Academic Review]<br>
            <span style="color: #475569;">[学术点评]：2026年最新随访确认，[[安圣莎]]辅助治疗不仅显著延长DFS，更展现了预防中枢神经系统复发的独特潜力。</span>
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            安圣莎 (Alecensa) · 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;">[[ALK]]•[[RET]]•[[LTK]]•[[STAT3]]•[[STAT5]]</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;">治疗领域</td>
                <td style="padding: 10px 15px; color: #334155;">[[ALK阳性肺癌]]•[[脑转移预防]]•[[术后辅助治疗]]</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;">竞争/序贯</td>
                <td style="padding: 10px 15px; color: #334155;">[[劳拉替尼]]•[[布格替尼]]•[[恩沙替尼]]•[[克唑替尼]]</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;">核心监测</td>
                <td style="padding: 10px 15px; color: #334155;">[[CPK水平]]•[[肝功能]]•[[脑部影像评价]]•[[ctDNA突变]]</td>
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