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Entrectinib - 版本历史
2026-04-18T03:48:46Z
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2026-01-15T06:25:37Z
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<strong>[[恩曲替尼]]</strong>（<strong>[[Entrectinib]]</strong>）是一种强效、口服的[[中枢神经系统]]（[[CNS]]）活性<strong>[[酪氨酸激酶抑制剂]]</strong>（[[TKI]]）。它是全球首批获准用于<strong>[[广谱抗癌]]</strong>（[[Tumor-agnostic]]）治疗的药物之一，主要靶向<strong>[[神经营养因子受体酪氨酸激酶]]</strong>（<strong>[[NTRK1/2/3]]</strong>）、<strong>[[ROS1]]</strong>及<strong>[[ALK]]</strong>融合蛋白。[[恩曲替尼]]通过竞争性结合激酶结构域的[[ATP]]位点，阻断下游[[信号转导]]，从而抑制携带相关基因融合的肿瘤生长。其独特的化学结构使其具备极佳的[[血脑屏障]]穿透能力，在治疗[[脑转移]]瘤及原发性[[中枢神经系统肿瘤]]中展现了显著价值。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">[[恩曲替尼]]</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px;">[[NTRK]] / [[ROS1]] / [[ALK]] · 点击展开详情</div><br />
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<div style="padding: 12px; border: 1px solid #e2e8f0; border-radius: 8px; background: #fff; display: inline-block;"><br />
<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;">[[恩曲替尼]]与激酶域结合模型</div><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心靶点：[[NTRK]] / [[ROS1]]</div><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%;">[[Entrez]]ID</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">4914/4915/4916</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[HGNC]]ID</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">8031/8032/8033</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[UniProt]]</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P04629/Q16620</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[分子量]]</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">560.6g/mol</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">药物分类</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[广谱靶向药物]]</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569;">原研厂商</th><br />
<td style="padding: 12px; color: #0f172a;">[[罗氏]]([[Roche]])</td><br />
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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：精准截断癌性信号</h2><br />
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[[恩曲替尼]]的作用原理基于对异常活跃的[[酪氨酸激酶]]的精准抑制，其核心分子逻辑如下：<br />
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<li style="margin-bottom: 12px;"><strong>[[激酶活性抑制]]：</strong>[[恩曲替尼]]竞争性占据[[TRKA/B/C]]、[[ROS1]]及[[ALK]]蛋白中的[[ATP]]结合口袋，阻止[[自身磷酸化]]，从而切断由[[SHC]]、[[RAS/RAF/MEK]]及[[PI3K/AKT]]驱动的肿瘤[[细胞增殖]]信号。</li><br />
<li style="margin-bottom: 12px;"><strong>[[血脑屏障]]高渗透性：</strong>通过分子结构优化，[[恩曲替尼]]在[[脑组织]]中维持较高的有效药物浓度，能够有效清除[[颅内转移]]病灶，这是其区别于同类药物（如[[拉罗替尼]]）的关键临床优势。</li><br />
<li style="margin-bottom: 12px;"><strong>针对[[融合基因]]：</strong>该药物对由[[染色体重排]]产生的[[TRK]]融合蛋白具有极高的选择性。这种融合通常出现在多种儿童及成人罕见实体瘤中。</li><br />
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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;">核心临床研究与适应症</h2><br />
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<th style="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">研究项目</th><br />
<th style="padding: 10px; border: 1px solid #cbd5e1; color: #475569;">适应症分层</th><br />
<th style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">客观缓解率 ([[ORR]])</th><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[STARTRK-2]]</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">[[NTRK]]融合阳性实性肿瘤 ([[广谱]])</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">约57% - 62% (包含多种瘤种)</td><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[ALKA-372-001]]</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">[[ROS1]]阳性[[NSCLC]]</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">约77% (初治患者获益更显著)</td><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[CNS]]子研究</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">伴有[[脑转移]]的肿瘤患者</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">颅内缓解率可达约50%以上</td><br />
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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：精准检测与安全性平衡</h2><br />
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[[恩曲替尼]]的成功应用高度依赖于早期[[分子画像]]与全病程的不良反应监控：<br />
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<li style="margin-bottom: 12px;"><strong>[[基因检测]]分层：</strong>推荐所有晚期实性肿瘤患者通过[[NGS]]（[[二代测序]]）或[[FISH]]检测[[NTRK]]融合及[[ROS1]]重排，以筛选[[广谱治疗]]获益人群。</li><br />
<li style="margin-bottom: 12px;"><strong>[[神经毒性]]监控：</strong>由于其较强的[[CNS]]活性，常见不良反应包含头晕、感觉异常及认知障碍。建议在用药初期由[[神经内科]]协作评估。</li><br />
<li style="margin-bottom: 12px;"><strong>[[心脏毒性]]预防：</strong>需关注[[QT间期延长]]及[[心力衰竭]]风险，用药期间应常规行[[超声心动图]]监测。</li><br />
<li style="margin-bottom: 12px;"><strong>[[获得性耐药]]对策：</strong>一旦出现耐药（如[[NTRK]]激酶域[[G595R]]或[[G667C]]突变），需考虑序贯[[第二代TRK-TKI]]（如[[瑞普替尼]]）。</li><br />
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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;">关键相关概念</h2><br />
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<li style="margin-bottom: 8px;"><strong>[[NTRK融合]]：</strong>一种罕见的强力驱动因子，存在于[[分泌型乳腺癌]]、[[婴儿纤维肉瘤]]及多种常见癌症的亚群中。</li><br />
<li style="margin-bottom: 8px;"><strong>[[广谱抗癌药]]：</strong>指根据肿瘤的[[分子特征]]而非[[发病解剖部位]]进行治疗的一类创新药物。</li><br />
<li style="margin-bottom: 8px;"><strong>[[ROS1]]：</strong>一种跨膜[[受体酪氨酸激酶]]，在约1-2%的[[非小细胞肺癌]]患者中发生重排。</li><br />
<li style="margin-bottom: 8px;"><strong>[[拉罗替尼]]：</strong>全球首个上市的[[TRK-TKI]]，是[[恩曲替尼]]在广谱治疗领域的主要竞争者。</li><br />
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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><br />
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[1] <strong>Drilon A, et al. (2020).</strong> <em>Entrectinib in ROS1-fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1–2 trials.</em> <strong>[[The Lancet Oncology]]</strong>.[Academic Review]<br><br />
<span style="color: #475569;">[权威点评]：该项整合分析确立了恩曲替尼在ROS1阳性肺癌及其脑转移治疗中的领先地位。</span><br />
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[2] <strong>Doebele RC, et al. (2020).</strong> <em>Entrectinib in patients with advanced or metastatic NTRK-fusion-positive solid tumours: integrated analysis of ALKA-372-001, STARTRK-1 and STARTRK-2 trials.</em> <strong>[[The Lancet Oncology]]</strong>.<br><br />
<span style="color: #475569;">[临床价值]：本研究支持了恩曲替尼作为“不限癌种”靶向疗法的全球监管批准。</span><br />
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[[恩曲替尼]] ([[Entrectinib]]) 诊疗生态 · 知识图谱<br />
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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><br />
<td style="padding: 10px 15px; color: #334155;">[[NTRK1]]•[[NTRK2]]•[[NTRK3]]•[[ROS1]]•[[ALK]]</td><br />
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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><br />
<td style="padding: 10px 15px; color: #334155;">[[不限癌种治疗]]•[[肺腺癌]]•[[结直肠癌]]•[[脑转移瘤]]</td><br />
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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;">竞争对手</td><br />
<td style="padding: 10px 15px; color: #334155;">[[拉罗替尼]]•[[克唑替尼]]•[[瑞普替尼]]•[[劳拉替尼]]</td><br />
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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;">研究前沿</td><br />
<td style="padding: 10px 15px; color: #334155;">[[针对儿童脑肿瘤的疗效评估]]•[[耐药点突变分子演变研究]]•[[联合免疫检查点方案探索]]</td><br />
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