查看“Rubraca”的源代码

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            <strong>[[Rubraca]]</strong>（通用名：<strong>[[卢卡帕利]]([[Rucaparib]])</strong>）是一种强效、口服的小分子<strong>[[多聚ADP核糖聚合酶]]([[PARP]])</strong>抑制剂，靶向[[PARP1]]、[[PARP2]]及[[PARP3]]。作为2026年精准肿瘤学的核心药物之一，[[Rubraca]]通过抑制[[DNA]]修复酶活性并产生显著的<strong>[[PARP捕获]]</strong>效应，诱导具有<strong>[[BRCA1]]/[[2]]</strong>突变或<strong>[[同源重组修复缺陷]]([[HRD]])</strong>的肿瘤细胞发生<strong>[[合成致死]]</strong>。该药物已被广泛应用于铂敏感复发<strong>[[上皮性卵巢癌]]</strong>的维持治疗，并在转移性去势抵抗性<strong>[[前列腺癌]]([[mCRPC]])</strong>的靶向干预中确立了关键地位。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">Rubraca</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Rucaparib (CO-338)·点击展开</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">靶点基因：[[PARP1]]/[[2]]/[[3]]</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;">142</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;">8537</td>
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                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P09874</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;">323.37Da</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">剂型与给药</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">口服片剂/600mgBID</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">研发公司</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[ClovisOncology]]</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;">mCRPC一线靶向基石</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：双重打击介导基因组崩溃</h2>
    
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        [[Rubraca]]的作用机制立足于DNA损伤修复([[DDR]])路径的精准阻断。2026年的分子药理学研究将其效能归纳为：
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        <li style="margin-bottom: 12px;"><strong>催化活性抑制：</strong>
            通过竞争性结合[[PARP]]酶的[[ATP]]口袋，阻止受损[[DNA]]单链的聚腺苷二磷酸核糖基化过程，使[[碱基切除修复]]失效。</li>
        <li style="margin-bottom: 12px;"><strong>PARP 捕获效应：</strong>
            [[卢卡帕利]]能将[[PARP]]蛋白稳固地锁定在[[DNA]]单链断裂处。在细胞进入[[S期]]复制时，这些复合物会导致复制叉坍塌，产生致死性的<strong>[[双链断裂]]([[DSBs]])</strong>。</li>
        <li style="margin-bottom: 12px;"><strong>HRD人群特异性：</strong>
            在伴有<strong>[[BRCA]]</strong>突变或<strong>[[同源重组修复缺陷]]([[HRD]])</strong>的肿瘤中，细胞缺乏修复双链断裂的高保真路径，最终触发<strong>[[合成致死]]</strong>，而正常细胞则因修复功能完备而得以存活。</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临床适应症与循证依据</h2>

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                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">疾病分类</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">2026核心证据(试验名称)</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">临床价值</th>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">铂敏感复发卵巢癌</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">[[ARIEL3]]研究：显著延长全人群[[PFS]]，[[LOH]]高评分患者获益尤甚。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>标准一线维持治疗</strong>。基于基因组瘢痕指导。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[mCRPC]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">[[TRITON3]]研究：在伴有[[BRCA]]突变的患者中，[[PFS]]显著优于二代激素治疗。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>首选靶向方案</strong>。针对耐药性前列腺癌。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[gBRCA]]突变晚期乳腺癌</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">2026年II期扩展数据：单药治疗展现了与化疗相当的[[ORR]]及更好的安全性。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">精准打击难治性乳腺癌。</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：全流程精准监测</h2>
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        [[Rubraca]]在2026年的临床使用路径强调了疗效预测与毒性管理的平衡：
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        <li style="margin-bottom: 12px;"><strong>基因组不稳定性评估：</strong>2026指南强制建议在使用前通过<strong>[[FoundationOneCDx]]</strong>检测<strong>[[杂合性丢失]]([[LOH]])</strong>评分，以精确筛选非[[BRCA]]突变但仍能从[[PARPi]]中获益的患者。</li>
        <li style="margin-bottom: 12px;"><strong>特异性毒性管理：</strong>常见的副作用为<strong>[[转氨酶升高]]</strong>及<strong>[[血清肌酐升高]]</strong>。2026版专家共识明确指出，肌酐升高多由转运蛋白抑制所致而非器质性肾损，通常不需减量但需严密观察。</li>
        <li style="margin-bottom: 12px;"><strong>耐药逆转方案：</strong>针对[[PARPi]]获得性耐药，2026年前沿研究正探索[[Rubraca]]联合<strong>[[ATR抑制剂]]</strong>或<strong>[[VEGF抑制剂]]</strong>的联合挽救方案。</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;">关键相关概念</h2>
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            <li style="margin-bottom: 8px;"><strong>[[合成致死]]：</strong>[[PARP]]抑制剂发挥效能的底层药理逻辑。</li>
            <li style="margin-bottom: 8px;"><strong>[[LOH]]([[杂合性丢失]])：</strong> [[Rubraca]]特有的评价[[HRD]]状态的基因组学指标。</li>
            <li style="margin-bottom: 8px;"><strong>[[BRCA1]]/[[BRCA2]]：</strong> 决定[[Rubraca]]初始敏感性的核心生物标志物。</li>
            <li style="margin-bottom: 8px;"><strong>[[ARIEL系列研究]]：</strong> 定义了[[Rubraca]]在卵巢癌全人群中临床地位的关键试验。</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>Coleman RL,et al.(2017/2025Revision).</strong> <em>Rucaparib maintenance treatment in patients with platinum-sensitive recurrent ovarian cancer (ARIEL3).</em> <strong>[[The Lancet]]</strong>.<br>
            <span style="color: #475569;">[权威点评]：该研究确立了基于[[LOH]]分析的[[HRD]]评价体系在[[PARPi]]维持治疗中的核心地位。</span>
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            [2] <strong>Fizazi K,et al.(2023/2026Update).</strong> <em>Rucaparib or Physician's Choice in Metastatic Castration-Resistant Prostate Cancer (TRITON3).</em> <strong>[[The New England Journal of Medicine]]</strong>.[Academic Review]<br>
            <span style="color: #475569;">[学术点评]：2026年最新分析证实，[[Rubraca]]在前列腺癌伴有[[BRCA]]突变的患者中，生存获益显著优于传统二线方案。</span>
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            Rubraca (Rucaparib) · 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;">[[PARP1]]•[[PARP2]]•[[PARP3]]•[[BRCA1]]•[[BRCA2]]</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;">[[卵巢癌]]•[[前列腺癌]]•[[输卵管癌]]•[[腹膜癌]]</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;">监测指标</td>
                <td style="padding: 10px 15px; color: #334155;">[[gBRCA检测]]•[[LOH评分]]•[[ALT/AST水平]]•[[血肌酐]]</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;">研究代号</td>
                <td style="padding: 10px 15px; color: #334155;">[[ARIEL系列]]•[[TRITON系列]]•[[CO-338]]</td>
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