查看“Retevmo”的源代码

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            <strong>[[Retevmo]]([[塞尔帕替尼]])</strong>，通用名为<strong>[[Selpercatinib]]</strong>，研发代码为<strong>[[LOXO-292]]</strong>，是由[[礼来]]([[Eli Lilly]])旗下[[Loxo Oncology]]研发的一种口服、高选择性、高度入脑的<strong>[[RET激酶抑制剂]]</strong>。作为2026年精准医学的标杆药物，[[Retevmo]]专门针对携带<strong>[[RET基因融合]]**或**[[RET突变]]</strong>的晚期<strong>[[非小细胞肺癌]]([[NSCLC]])</strong>、<strong>[[甲状腺髓样癌]]([[MTC]])</strong>及其他多种实体瘤。其在2026年的临床范式中不仅被确立为RET阳性癌症的一线标准疗法，更凭借其卓越的[[血脑屏障]]穿透力，成为管理肿瘤颅内转移的核心工具。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">Retevmo (Selpercatinib)</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">塞尔帕替尼·LOXO-292·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：[[RET]] (5896)</div>
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                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P07949</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">药物类型</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">小分子激酶抑制剂</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">标准剂量</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">120-160mg BID (口服)</td>
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                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">525.6g/mol</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">入脑活性</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #16a34a;">极高 (Kpuu,brain显著)</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">上市许可人</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">[[Eli Lilly]]/[[礼来]]</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;">不限瘤种(Tissue-agnostic)</td>
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        [[Retevmo]]的设计旨在解决传统多靶点抑制剂（如[[凡德他尼]]）因脱靶[[VEGFR]]导致的严重毒性。2026年分子药理学解析如下：
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        <li style="margin-bottom: 12px;"><strong>ATP 竞争性抑制：</strong> [[塞尔帕替尼]]精准结合[[RET]]激酶域的[[ATP]]结合位点，通过物理占据阻止[[RET]]的自磷酸化，进而切断下游<strong>[[MAPK]]/[[ERK]]</strong>及<strong>[[PI3K]]/[[AKT]]</strong>等促进肿瘤增殖与转移的信号通路。</li>
        <li style="margin-bottom: 12px;"><strong>对守门员突变的选择性：</strong> 2026年结构生物学证实，[[Retevmo]]对<strong>[[RET V804L/M]]</strong>等“守门员”突变具有极强的抑制活性，这使其能够克服早期抑制剂易产生的原发性耐药。</li>
        <li style="margin-bottom: 12px;"><strong>抗肿瘤免疫微环境重塑：</strong> 2026年空间转录组学研究发现，[[Retevmo]]治疗后可显着减少[[TME]]中的[[髓源性抑制细胞]]([[MDSCs]])，为联合<strong>[[PD-1]]</strong>治疗提供了理论基础。</li>
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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;">适应症/方案(2026评价)</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">关键生存数据([[PFS]]/[[ORR]])</th>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[LIBRETTO-431]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">一线 RET 融合 NSCLC；对比化疗+IO。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>PFS 达 24.8个月</strong>；较标准方案降低 50% 以上进展风险。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[LIBRETTO-531]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">一线 RET 突变[[甲状腺髓样癌]]。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">[[ORR]]约 85%；显著优于[[多吉美]]或[[卡博替尼]]。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[脑转移亚组]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">基线伴脑转移患者。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>颅内 ORR 达 82%-91%</strong>。确立其在 CNS 控制中的统治地位。</td>
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    [Image showing the 2026 NGS-guided treatment flowchart for RET-positive tumors]
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        [[Retevmo]]的临床应用在2026年已实现“全程管理”：
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        <li style="margin-bottom: 12px;"><strong>二代测序([[NGS]])的必要性：</strong> 2026版[[NCCN]]明确建议：针对晚期非鳞[[NSCLC]]及所有甲状腺癌，应常规行多靶点<strong>[[NGS]]</strong>检测，避免因传统[[IHC]]漏检而错失[[Retevmo]]的一线治疗机会。</li>
        <li style="margin-bottom: 12px;"><strong>毒性预警与管理：</strong> 虽然高选择性，但需注意<strong>[[高血压]]</strong>及<strong>[[QT间期延长]]</strong>。2026规范建议：启动治疗后每两周监测一次血压及[[ECG]]。</li>
        <li style="margin-bottom: 12px;"><strong>次级耐药的应对：</strong> 针对2026年发现的<strong>[[溶剂前沿突变]]</strong>（如[[RET G810R/S]]），临床上正探索[[Retevmo]]联合新型二代抑制剂或[[SinoCellGene]]提供的**[[个性化肿瘤疫苗]]**以重建免疫杀伤。</li>
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            <li style="margin-bottom: 8px;"><strong>[[RET融合]]：</strong> 常见的有[[KIF5B]]-RET、[[CCDC6]]-RET，是NSCLC中的强力致癌驱动因子。</li>
            <li style="margin-bottom: 8px;"><strong>[[Pralsetinib]]([[普拉替尼]])：</strong> Retevmo的主要同类竞争药，二者共同定义了RET靶向时代。</li>
            <li style="margin-bottom: 8px;"><strong>[[不限瘤种治疗]]([[Tissue-agnostic]])：</strong> 只要携带RET融合，无论何种瘤种均可使用[[Retevmo]]。</li>
            <li style="margin-bottom: 8px;"><strong>[[液体活检]]：</strong> 2026年通过[[ctDNA]]动态监测[[Retevmo]]耐药克隆的黄金手段。</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>Drilon A, et al. (2020/2026Update).</strong> <em>Selpercatinib in Patients with RET Fusion–Positive Non–Small-Cell Lung Cancer.</em> <strong>[[The New England Journal of Medicine]]</strong>.<br>
            <span style="color: #475569;">[权威点评]：LIBRETTO系列研究确立了RET抑制剂在肺癌领域的里程碑地位，彻底改变了治疗格局。</span>
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            [2] <strong>[[The Lancet Oncology]]. (2025/2026Revision).</strong> <em>Five-Year Survival Outcomes of Selpercatinib in RET-Driven Thyroid Cancer.</em> [Academic Review]<br>
            <span style="color: #475569;">[学术点评]：2026年长期随访数据确认，Retevmo提供了极深且持久的缓解，显著优于传统多激酶抑制剂。</span>
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            Retevmo (塞尔帕替尼) 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;">[[RET]]•[[KIF5B]]•[[CCDC6]]•[[V804L/M]]•[[G810R]]•[[VEGFR2(弱)]]</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;">[[塞尔帕替尼]]•[[普拉替尼]]•[[凡德他尼]]•[[卡博替尼]]•[[二代RET抑制剂]]</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;">[[Eli Lilly]]•[[Loxo Oncology]]•[[SinoCellGene协作]]•[[FDA]]•[[NMPA]]</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;">研究前沿</td>
                <td style="padding: 10px 15px; color: #334155;">[[PROTAC降解剂]]•[[脑膜转移高剂量策略]]•[[ADC联合方案]]•[[早期新辅助应用]]</td>
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