查看“Olaparib”的源代码

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            <strong>[[奥拉帕利]]</strong>（<strong>[[Olaparib]]</strong>，商品名 <strong>[[利普卓]]</strong> / <strong>[[Lynparza]]</strong>）是一种首创的（First-in-class）、口服强效 <strong>[[多聚ADP核糖聚合酶]]</strong>（<strong>[[PARP]]</strong>）抑制剂。它通过利用 <strong>[[合成致死]]</strong>（<strong>[[Synthetic Lethality]]</strong>）的生物学原理，特异性诱导具有 <strong>[[同源重组修复]]</strong>（<strong>[[HRR]]</strong>）缺陷（如 <strong>[[BRCA1]]</strong> 或 <strong>[[BRCA2]]</strong> 基因突变）的肿瘤细胞 <strong>[[凋亡]]</strong>。自 2014 年获批以来，<strong>[[奥拉帕利]]</strong> 已从 <strong>[[卵巢癌]]</strong> 扩展至 <strong>[[乳腺癌]]</strong>、<strong>[[胰腺癌]]</strong> 及 <strong>[[前列腺癌]]</strong>，成为 <strong>[[精准肿瘤学]]</strong> 中针对 <strong>[[DNA 损伤修复]]</strong>（<strong>[[DDR]]</strong>）通路的标杆性药物。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">奥拉帕利</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px;">Drug: [[Olaparib]] ([[Lynparza]]) · 点击展开详情</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">[[合成致死]]抗癌药</div>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 45%;">核心靶标</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0; color: #b91c1c;"><strong>[[PARP1]] / [[PARP2]]</strong></td>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">Entrez ID (Target)</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0;">142 (PARP1)</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 (Target)</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0;">270 (PARP1)</td>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">UniProt ID</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0;">P09874 (PARP1)</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;">434.46 Da</td>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">CAS 登记号</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0;">763113-22-0</td>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569;">给药途径</th>
                    <td style="padding: 10px 12px;">[[口服]] (BID)</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;">致病机制与药理逻辑：双重阻断 DNA 修复</h2>
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        <strong>[[奥拉帕利]]</strong> 的核心机制在于利用肿瘤细胞的 <strong>[[同源重组修复]]</strong>（<strong>[[HR]]</strong>）通路缺陷，构建“绝路”：
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        <li style="margin-bottom: 12px;"><strong>抑制单链修复：</strong> <strong>[[PARP]]</strong> 酶在识别 DNA <strong>[[单链断裂]]</strong>（<strong>[[SSB]]</strong>）并启动 <strong>[[碱基切除修复]]</strong> 中起关键作用。<strong>[[奥拉帕利]]</strong> 阻断此过程，使 SSB 累积并转化为 <strong>[[双链断裂]]</strong>（<strong>[[DSB]]</strong>）。</li>
        <li style="margin-bottom: 12px;"><strong>PARP 捕获效应：</strong> 药物能将 <strong>[[PARP]]</strong> 酶锁定在 DNA 损伤位点，形成的复合物阻碍了 <strong>[[DNA 复制叉]]</strong> 的推进，加剧基因组压力。</li>
        <li style="margin-bottom: 12px;"><strong>合成致死：</strong> 携带 <strong>[[BRCA1/2]]</strong> 突变的细胞无法通过 <strong>[[同源重组]]</strong> 修复 DSB，只能求助于易错的 <strong>[[非同源末端连接]]</strong>（<strong>[[NHEJ]]</strong>），最终导致 <strong>[[染色体]]</strong> 灾难性损伤而死亡。</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;">临床图谱：核心适应症与关键研究</h2>
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                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 20%;">癌症类型</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">关键试验 (Key Trials)</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">治疗地位</th>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[卵巢癌]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>[[SOLO-1]]</strong> / [[PAOLA-1]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">一线维持治疗，针对 <strong>[[BRCA]]</strong> 突变或 <strong>[[HRD]]</strong> 阳性。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[乳腺癌]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>[[OlympiAD]]</strong> / [[OlympiA]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>[[gBRCAm]]</strong> 转移性乳腺癌及早期高危术后辅助。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[前列腺癌]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>[[PROfound]]</strong> / [[PROpel]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">携带 <strong>[[HRR]]</strong> 突变的 <strong>[[mCRPC]]</strong>。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[胰腺癌]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>[[POLO]]</strong></td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>[[gBRCAm]]</strong> 转移性胰腺癌的一线维持治疗。</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;">治疗策略：基于 HRD 的精准决策</h2>
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        <li style="margin-bottom: 12px;"><strong>伴随诊断：</strong> 在启动 <strong>[[奥拉帕利]]</strong> 治疗前，必须进行 <strong>[[BRCA1/2]]</strong> 基因检测或 <strong>[[同源重组修复缺陷]]</strong>（<strong>[[HRD]]</strong>）评分，以确定潜在获益程度。</li>
        <li style="margin-bottom: 12px;"><strong>维持治疗模式：</strong> 在 <strong>[[含铂化疗]]</strong> 缓解后立即启动维持治疗，旨在极大限度延长无病生存期。</li>
        <li style="margin-bottom: 12px;"><strong>毒性管理：</strong> 常见副作用包括 <strong>[[贫血]]</strong>、<strong>[[恶心]]</strong> 及 <strong>[[骨髓抑制]]</strong>。需定期监测 <strong>[[全血细胞计数]]</strong>，并根据 <strong>[[CTCAE]]</strong> 分级调整剂量。</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;">[[合成致死]]</strong>：<strong>[[奥拉帕利]]</strong> 作用的底层逻辑。</div>
            <div style="color: #334155;"><strong style="color: #1e40af;">[[BRCA1]] / [[BRCA2]]</strong>：<strong>[[抑癌基因]]</strong>，其功能缺失使细胞对 <strong>[[PARP 抑制剂]]</strong> 敏感。</div>
            <div style="color: #334155;"><strong style="color: #1e40af;">[[HRD]]</strong>：比 <strong>[[BRCA]]</strong> 更广谱的 <strong>[[同源重组]]</strong> 缺陷指标。</div>
            <div style="color: #334155;"><strong style="color: #1e40af;">[[铂类敏感]]</strong>：临床预测 <strong>[[奥拉帕利]]</strong> 响应度的核心临床指标。</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>Moore K, et al. (2018).</strong> <em>Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer.</em> <strong>[[The New England Journal of Medicine]]</strong>.<br>
            <span style="color: #475569;">[学术点评]：SOLO-1 研究里程碑式地证实了一线维持治疗对 <strong>[[BRCA]]</strong> 突变卵巢癌患者的革命性获益。</span>
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        <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;">
            [2] <strong>Robson M, et al. (2017).</strong> <em>Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation.</em> <strong>[[The New England Journal of Medicine]]</strong>.<br>
            <span style="color: #475569;">[学术点评]：OlympiAD 研究确立了 <strong>[[奥拉帕利]]</strong> 在遗传性乳腺癌 <strong>[[精准治疗]]</strong> 中的核心地位。</span>
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            奥拉帕利 ([[Olaparib]]) · 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;">分子属性</td>
                <td style="padding: 10px 15px; color: #334155; text-align: left;">[[PARP1 抑制]] • [[DNA 修复阻断]] • [[合成致死]] • [[HRD 靶向]]</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;">临床适应症</td>
                <td style="padding: 10px 15px; color: #334155; text-align: left;">[[卵巢癌]] • [[gBRCAm 乳腺癌]] • [[转移性胰腺癌]] • [[mCRPC]]</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;">同类药物</td>
                <td style="padding: 10px 15px; color: #334155; text-align: left;">[[尼拉帕利]] (Niraparib) • [[氟唑帕利]] • [[帕米帕利]] • [[卢卡帕利]]</td>
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