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BRCA1 - 版本历史
2026-04-19T08:51:44Z
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2026年1月23日 (五) 12:23 77921020
2026-01-23T12:23:09Z
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">2026年1月23日 (五) 12:23的版本</td>
</tr><tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l54" >第54行：</td>
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2026年1月23日 (五) 12:18 77921020
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<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> [4] <strong>Moore K, Colombo N, Scambia G, et al. (2018).</strong> <em>Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer.</em> <strong>[[New England Journal of Medicine]]</strong>. 2018;379(26):2495-2505.<br></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> [4<ins class="diffchange diffchange-inline">] <strong>Robson M, Im SA, Senkus E, et al. (2017).</strong> <em>Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation.</em> <strong>[[New England Journal of Medicine]]</strong>. 2017;377(6):523-533.<br></ins></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <span style="color: #475569;">[学术点评]：SOLO-1 研究。证实了奥拉帕利在 BRCA 突变晚期卵巢癌一线维持治疗中的惊人疗效（降低 70% <del class="diffchange diffchange-inline">进展风险），改变了卵巢癌的治疗指南。</del></span></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> <span style="color: #475569;">[学术点评]：OlympiAD 研究。这是首个证明 PARP 抑制剂（奥拉帕利）在 HER2 阴性、生殖系 BRCA 突变转移性乳腺癌中疗效优于标准单药化疗的 III 期临床试验，促成了药物获批。</span></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> </p></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> </div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> [5</ins>] <strong>Moore K, Colombo N, Scambia G, et al. (2018).</strong> <em>Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer.</em> <strong>[[New England Journal of Medicine]]</strong>. 2018;379(26):2495-2505.<br></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <span style="color: #475569;">[学术点评]：SOLO-1 研究。证实了奥拉帕利在 BRCA 突变晚期卵巢癌一线维持治疗中的惊人疗效（降低 70% <ins class="diffchange diffchange-inline">进展风险），彻底改变了卵巢癌的治疗指南。</span></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> </p></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> </div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> [6] <strong>Golan T, Hammel P, Reni M, et al. (2019).</strong> <em>Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer.</em> <strong>[[New England Journal of Medicine]]</strong>. 2019;381(4):317-327.<br></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> <span style="color: #475569;">[学术点评]：POLO 研究。将 BRCA1/2 靶向治疗扩展到了胰腺癌领域，证明了在接受铂类化疗未进展的胚系 BRCA 突变胰腺癌患者中，奥拉帕利维持治疗可延长 PFS。</span></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> </p></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> </div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> <p style="margin: 12px 0;"></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> [7] <strong>Roy R, Chun J, Powell SN. (2011).</strong> <em>BRCA1 and BRCA2: different roles in a common pathway of genome protection.</em> <strong>[[Nature Reviews Cancer]]</strong>. 2011;12(1):68-78.<br></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> <span style="color: #475569;">[学术点评]：权威综述。系统比较了 BRCA1 和 BRCA2 在同源重组修复、细胞周期检查点及转录调控中的不同角色，是理解两者功能差异及协同作用的经典文献。</ins></span></div></td></tr>
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2026年1月23日 (五) 12:15 77921020
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<strong>BRCA1</strong>（Breast Cancer Type 1 Susceptibility Protein），全称为 <strong>乳腺癌易感基因 1</strong>，是人类最重要的 <strong>[[抑癌基因]]</strong> 之一。BRCA1 编码的蛋白是 DNA 双链断裂修复系统中的核心支架，通过高保真的 <strong>[[同源重组]]</strong>（Homologous Recombination, HR）途径维护基因组稳定性。BRCA1 的胚系突变（Germline Mutation）是导致 <strong>[[遗传性乳腺癌-卵巢癌综合征]]</strong>（HBOC）的主要原因，携带者一生中患乳腺癌和卵巢癌的风险显著高于常人。在治疗领域，BRCA1 突变导致的“同源重组缺陷”（HRD）使其成为 <strong>[[合成致死]]</strong> 疗法（如 PARP 抑制剂）的经典靶标。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">BRCA1 · 基因档案</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Gene & Protein Profile (点击展开)</div><br />
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[[文件:Protein_BRCA1_BRCT_PDB_1JNX.png|100px|BRCA1 BRCT 结构域 (PDB 1JNX)]]<br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">DNA 修复核心支架</div><br />
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<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc; width: 40%;">基因符号</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #0f172a;"><strong>BRCA1</strong></td><br />
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<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">Breast Cancer Type 1 Susceptibility Protein</td><br />
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<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">常用别名</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">RNF53, IRIS, PSCP</td><br />
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<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">染色体位置</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">17q21.31</td><br />
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<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">Entrez</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">672</td><br />
</tr><br />
<tr><br />
<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">HGNC</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">1100</td><br />
</tr><br />
<tr><br />
<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">OMIM</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">113705</td><br />
</tr><br />
<tr><br />
<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">UniProt</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">P38398</td><br />
</tr><br />
<tr><br />
<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">功能分类</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">DNA 修复 / E3 连接酶</td><br />
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<tr><br />
<th style="text-align: left; padding: 8px 12px; color: #475569; background-color: #f8fafc;">分子量</th><br />
<td style="padding: 8px 12px; color: #0f172a;">~220 kDa</td><br />
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</table><br />
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</div><br />
<br />
<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：基因组的精准修复师</h2><br />
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<p style="margin: 15px 0; text-align: justify;"><br />
BRCA1 是一种多功能的大分子蛋白，它主要通过与 <strong>[[BARD1]]</strong> 形成异二聚体来发挥 E3 泛素连接酶活性，并招募其他修复因子（如 PALB2 和 BRCA2）至 DNA 损伤位点。<br />
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<ul style="padding-left: 25px; color: #334155;"><br />
<li style="margin-bottom: 12px;"><strong>同源重组 (HR) 修复：</strong> 当 DNA 发生双链断裂（DSB）时，BRCA1 是启动“无错修复”的关键。它帮助细胞利用未受损的姐妹染色单体作为模板，精确修复断裂的 DNA，防止遗传信息丢失。</li><br />
<li style="margin-bottom: 12px;"><strong>同源重组缺陷 (HRD)：</strong> 当 BRCA1 突变导致其功能丧失时，细胞被迫使用低保真的修复途径（如非同源末端连接 NHEJ），导致基因组极其不稳定，这既是致癌原因，也是治疗的“软肋”。</li><br />
</ul><br />
<br />
<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;">临床景观：HBOC 综合征的核心</h2><br />
<p style="margin: 15px 0; text-align: justify;"><br />
BRCA1 突变携带者面临着极高的终生患癌风险，这种遗传倾向被称为<strong>遗传性乳腺癌-卵巢癌综合征 (HBOC)</strong>。与 BRCA2 相比，BRCA1 突变相关乳腺癌具有独特的病理特征。<br />
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<div style="overflow-x: auto; margin: 30px auto; max-width: 90%;"><br />
<table style="width: 100%; border-collapse: collapse; border: 1.2px solid #cbd5e1; font-size: 0.95em; text-align: left;"><br />
<tr style="background-color: #f8fafc; border-bottom: 2px solid #0f172a;"><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">癌种类型</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">终生风险 / 特征</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">临床意义</th><br />
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<tr><br />
<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">乳腺癌</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">风险 <strong>65-80%</strong><br>多为 <strong>[[三阴性乳腺癌]]</strong> (TNBC)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">发病年龄早。由于缺乏 ER/PR/HER2 表达，激素和 HER2 靶向治疗无效，主要依赖化疗和 PARP 抑制剂。预防性乳腺切除可降低 90% 风险。</td><br />
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<tr><br />
<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">卵巢癌</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">风险 <strong>39-44%</strong><br>多为高级别浆液性癌</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">预后凶险，缺乏有效筛查手段。推荐完成生育后（约 35-40 岁）进行预防性输卵管-卵巢切除术（RRSO）。</td><br />
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<tr><br />
<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">前列腺癌</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">风险增加 (~8-10%)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">虽然风险增幅不如 BRCA2 显著，但一旦发病，通常侵袭性更强，Gleason 评分更高。</td><br />
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<tr><br />
<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">胰腺癌</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">风险增加 (~2-3%)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">所有胰腺癌患者均建议进行种系 BRCA 检测，因为这关系到铂类化疗和 PARP 抑制剂的使用。</td><br />
</tr><br />
</table><br />
</div><br />
<br />
<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：合成致死与铂类敏感</h2><br />
<p style="margin: 15px 0; text-align: justify;"><br />
BRCA1 突变细胞对造成 DNA 双链断裂的因素极度敏感。临床上利用这一“阿喀琉斯之踵”开发了特定的治疗方案：<br />
</p><br />
<ul style="padding-left: 25px; color: #334155;"><br />
<li style="margin-bottom: 12px;"><strong>PARP 抑制剂（合成致死）：</strong> 如 <strong>[[奥拉帕利]]</strong> (Olaparib)、<strong>[[尼拉帕利]]</strong>。<br />
<br><span style="font-size: 0.9em; color: #64748b;">*原理：PARP 负责修复 DNA 单链断裂。抑制 PARP 会导致单链断裂转变为双链断裂。正常细胞可通过 BRCA 介导的 HR 修复，但 BRCA1 突变细胞无法修复，最终导致基因组崩溃死亡（合成致死）。</span><br />
</li><br />
<li style="margin-bottom: 12px;"><strong>铂类化疗：</strong> 如顺铂、卡铂。铂类药物引起 DNA 链间交联，高度依赖同源重组修复。因此，BRCA1 突变肿瘤通常对铂类药物表现出<strong>高度敏感性</strong>（Platinum-sensitive）。</li><br />
</ul><br />
<br />
<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;">关键关联概念</h2><br />
<ul style="padding-left: 25px; color: #334155;"><br />
<li style="margin-bottom: 12px;"><strong>同源重组缺陷 (HRD)：</strong> 一种基因组瘢痕特征，不仅由 BRCA 突变引起，其他 HR 通路基因异常也可导致。HRD 阳性是 PARP 抑制剂应用的重要指征。</li><br />
<li style="margin-bottom: 12px;"><strong>合成致死 (Synthetic Lethality)：</strong> 两个非致死基因同时失活导致细胞死亡的现象。PARP 抑制剂与 BRCA 突变是该机制在肿瘤学中最成功的应用。</li><br />
<li style="margin-bottom: 12px;"><strong>三阴性乳腺癌 (TNBC)：</strong> ER-、PR-、HER2- 的乳腺癌亚型，约 10-20% 的 TNBC 患者携带 BRCA1 胚系突变。</li><br />
<li style="margin-bottom: 12px;"><strong>预防性切除 (Prophylactic Surgery)：</strong> 针对 BRCA 突变携带者的降风险手术，包括双侧乳腺切除和输卵管-卵巢切除。</li><br />
</ul><br />
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<div style="font-size: 0.92em; line-height: 1.6; color: #1e293b; margin-top: 50px; border-top: 2px solid #0f172a; padding: 15px 25px; background-color: #f8fafc; border-radius: 0 0 10px 10px;"><br />
<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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<p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"><br />
[1] <strong>Hall JM, et al. (1990).</strong> <em>Linkage of early-onset familial breast cancer to chromosome 17q21.</em> <strong>Science</strong>. <br><br />
<span style="color: #475569;">[学术点评]：里程碑式发现，通过连锁分析首次将家族性乳腺癌基因定位到 17 号染色体，开启了 BRCA 研究时代。</span><br />
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<p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"><br />
[2] <strong>Miki Y, et al. (1994).</strong> <em>A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1.</em> <strong>Science</strong>. <br><br />
<span style="color: #475569;">[学术点评]：成功克隆并测序了 BRCA1 基因，确立了其作为 HBOC 综合征致病基因的地位。</span><br />
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<p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"><br />
[3] <strong>Farmer H, et al. (2005).</strong> <em>Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy.</em> <strong>Nature</strong>. <br><br />
<span style="color: #475569;">[学术点评]：首次阐明了 PARP 抑制剂在 BRCA 缺陷细胞中的“合成致死”效应，为 PARP 抑制剂的临床开发奠定了理论基础。</span><br />
</p><br />
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<p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"><br />
[4] <strong>Robson M, et al. (2017).</strong> <em>Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation.</em> <strong>New England Journal of Medicine</strong>. <br><br />
<span style="color: #475569;">[学术点评]：OlympiAD 研究。证实了奥拉帕利在 BRCA 突变转移性乳腺癌中的疗效优于标准化疗，标志着乳腺癌进入合成致死治疗时代。</span><br />
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<p style="margin: 12px 0;"><br />
[5] <strong>Moore K, et al. (2018).</strong> <em>Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer.</em> <strong>New England Journal of Medicine</strong>. <br><br />
<span style="color: #475569;">[学术点评]：SOLO-1 研究。显示奥拉帕利维持治疗使 BRCA 突变卵巢癌患者的无进展生存期（PFS）获得了史无前例的延长。</span><br />
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<div style="background-color: #0f172a; color: #ffffff; text-align: center; font-weight: bold; padding: 10px; letter-spacing: 1px;">BRCA1 · 知识图谱关联</div><br />
<div style="padding: 15px; background: #ffffff; line-height: 2.2; text-align: center; text-decoration: none;"><br />
[[BRCA2]] • [[PARP抑制剂]] • [[同源重组]] • [[HRD]] • [[奥拉帕利]] • [[三阴性乳腺癌]] • [[合成致死]] • [[卵巢癌]] • [[铂类敏感]]<br />
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