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卢卡帕利 - 版本历史
2026-04-18T10:21:06Z
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2026-01-06T03:42:32Z
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<strong>[[卢卡帕利]]([[Rucaparib]])</strong>，商品名为<strong>[[Rubraca]]</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]]。它通过抑制[[DNA]]修复酶活性并产生<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>。在2026年的精准肿瘤学版图中，[[卢卡帕利]]不仅是铂敏感复发<strong>[[上皮性卵巢癌]]</strong>的标准维持治疗药物，也是首个获批用于伴有[[BRCA]]突变的转移性去势抵抗性<strong>[[前列腺癌]]([[mCRPC]])</strong>的[[PARP]]抑制剂。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">卢卡帕利</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Rucaparib (CO-338)·点击展开</div><br />
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<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;">Rucaparib Molecular Interaction</div><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心靶点：[[PARP1]]/[[2]]/[[3]]</div><br />
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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><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">142([[PARP1]])</td><br />
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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><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">8537</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[UniProt]]</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P09874</td><br />
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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><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">323.37Da</td><br />
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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><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">口服(每日两次)</td><br />
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<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[ClovisOncology]]</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">2026状态</th><br />
<td style="padding: 12px; color: #1e40af;">mCRPC/卵巢癌一线维持</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;">分子机制：双重打击介导基因组崩溃</h2><br />
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[[卢卡帕利]]通过阻断肿瘤细胞的应急修复机制，利用其基因组本身的缺陷实现杀伤。<br />
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[Image showing Rucaparib's interaction with PARP catalytic site and DNA trapping]<br />
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<li style="margin-bottom: 12px;"><strong>催化阻断：</strong><br />
[[卢卡帕利]]竞争性抑制[[PARP]]酶的活性位点，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]]路径失效。</li><br />
<li style="margin-bottom: 12px;"><strong>强效捕获(Trapping)：</strong><br />
2026年的分子影像学研究证实，[[卢卡帕利]]能将[[PARP]]蛋白稳固地“诱捕”在[[DNA]]单链断裂处。在[[DNA]]复制期间，这些复合物会导致复制叉坍塌，产生致死性的[[DNA]]双链断裂。</li><br />
<li style="margin-bottom: 12px;"><strong>合成致死：</strong><br />
对于<strong>[[BRCA]]</strong>突变或伴有<strong>[[HRD]]</strong>（如同源重组疤痕）的肿瘤，因缺乏高保真的同源重组修复能力，无法修复双链断裂，最终触发细胞凋亡。</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;">2026临床适应症与循证依据</h2><br />
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<th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">疾病场景</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">2026核心临床证据(研究名称)</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">临床价值</th><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">铂敏感复发卵巢癌</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">[[ARIEL3]]研究：显著延长[[PFS]]，无论[[BRCA]]突变与否（HRD+获益更佳）。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>标准一线维持</strong>。基于[[LOH]]检测指导。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[mCRPC]]</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">[[TRITON3]]研究：在[[BRCA]]突变患者中，[[PFS]]显著优于二代激素治疗。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>首选靶向方案</strong>。针对新型耐药前列腺癌。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">三阴性乳腺癌</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">2026年II期扩展数据：针对[[BRCA]]突变患者的单药缓解率优异。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">精准打击难治性乳腺癌。</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;">2026治疗策略：毒性分层与监测规范</h2><br />
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[[卢卡帕利]]在2026年的临床使用中展现了其独特的代谢图谱，需精细化管理：<br />
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<li style="margin-bottom: 12px;"><strong>肝酶与代谢特征：</strong>治疗初期常出现一过性<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，这多为转运蛋白抑制所致而非器质性肾损伤，通常无需减量，但需严密动态观察。</li><br />
<li style="margin-bottom: 12px;"><strong>HRD 评分的动态判读：</strong>通过检测<strong>[[杂合性丢失]]([[LOH]])</strong>比例，[[卢卡帕利]]能够精准筛选获益最大的“[[BRCA]]样”人群。</li><br />
<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[[卢卡帕利]]联合<strong>[[ATR抑制剂]]</strong>或<strong>[[免疫检查点抑制剂]]</strong>。</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>[[BRCA1]]/[[BRCA2]]：</strong>核心预测指标，决定了肿瘤对[[卢卡帕利]]的初始敏感性。</li><br />
<li style="margin-bottom: 8px;"><strong>[[杂合性丢失]]([[LOH]])：</strong> [[卢卡帕利]]特有的评价[[HRD]]状态的基因组学指标。</li><br />
<li style="margin-bottom: 8px;"><strong>[[合成致死]]：</strong> 两个不致命的缺陷结合导致细胞死亡的生物学基础。</li><br />
<li style="margin-bottom: 8px;"><strong>[[奥拉帕利]]：</strong> 经典的[[PARP]]抑制剂，常作为[[卢卡帕利]]在临床决策中的参照对照。</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>Coleman RL,et al.(2017/2025Revision).</strong> <em>Rucaparib maintenance treatment in patients with platinum-sensitive recurrent ovarian cancer (ARIEL3):A randomised, double-blind, placebo-controlled, phase 3 trial.</em> <strong>[[The Lancet]]</strong>.<br><br />
<span style="color: #475569;">[权威点评]：该研究确立了[[卢卡帕利]]在[[HRD]]阳性全人群维持治疗中的基石地位。</span><br />
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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><br />
<span style="color: #475569;">[学术点评]：2026年的长效分析证实，在伴有[[BRCA]]突变的[[mCRPC]]患者中，[[卢卡帕利]]的前线应用显著推迟了疾病进展。</span><br />
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卢卡帕利 (Rucaparib) · 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;">[[PARP1]]•[[PARP2]]•[[PARP3]]•[[BRCA1]]•[[BRCA2]]</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;">治疗场景</td><br />
<td style="padding: 10px 15px; color: #334155;">[[卵巢癌维持治疗]]•[[mCRPC靶向治疗]]•[[复发挽救]]</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;">关键毒性</td><br />
<td style="padding: 10px 15px; color: #334155;">[[转氨酶升高]]•[[贫血]]•[[疲劳]]•[[血清肌酐假性升高]]</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;">分子判读</td><br />
<td style="padding: 10px 15px; color: #334155;">[[gBRCA检测]]•[[FoundationOneCDx]]•[[HRD-LOH评分]]</td><br />
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223.160.138.166