https://www.yiliao.com/index.php?action=history&feed=atom&title=FGFR2
FGFR2 - 版本历史
2026-04-18T11:00:34Z
本wiki的该页面的版本历史
MediaWiki 1.35.1
https://www.yiliao.com/index.php?title=FGFR2&diff=311622&oldid=prev
77921020：建立内容为“<div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff…”的新页面
2025-12-29T12:25:48Z
<p>建立内容为“<div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff…”的新页面</p>
<p><b>新页面</b></p><div><div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff; max-width: 1200px; margin: auto;"><br />
<br />
<div style="margin-bottom: 30px; border-bottom: 1.2px solid #e2e8f0; padding-bottom: 25px;"><br />
<p style="font-size: 1.1em; margin: 10px 0; color: #334155; text-align: justify;"><br />
<strong>FGFR2</strong>（Fibroblast Growth Factor Receptor 2），全称为 <strong>成纤维细胞生长因子受体 2</strong>，是 FGFR 家族中功能最为复杂的成员之一。其基因表达受到精细的<strong>[[可变剪接]]</strong>调控，产生两种关键亚型：主要表达于上皮细胞的 <strong>FGFR2b</strong> 和表达于间充质细胞的 <strong>FGFR2c</strong>，这种特异性表达对于维持上皮-间质相互作用至关重要。在病理状态下，FGFR2 具有高度的组织特异性致癌机制：在 <strong>[[肝内胆管癌]]</strong> 中主要是<strong>基因融合</strong>，在 <strong>[[胃癌]]</strong> 中主要是 <strong>FGFR2b 过表达/扩增</strong>，而在 <strong>[[Apert综合征]]</strong> 等骨发育疾病中则是<strong>胚系突变</strong>。<br />
</p><br />
</div><br />
<br />
<div class="medical-infobox mw-collapsible mw-collapsed" style="width: 100%; max-width: 320px; margin: 0 auto 35px auto; border: 1.2px solid #bae6fd; border-radius: 12px; background-color: #ffffff; box-shadow: 0 8px 20px rgba(0,0,0,0.05); overflow: hidden;"><br />
<br />
<div style="padding: 15px; color: #1e40af; background: linear-gradient(135deg, #e0f2fe 0%, #bae6fd 100%); text-align: center; cursor: pointer;"><br />
<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">FGFR2 · 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 />
</div><br />
<br />
<div class="mw-collapsible-content"><br />
<div style="padding: 25px; text-align: center; background-color: #f8fafc;"><br />
<div style="display: inline-block; background: #ffffff; border: 1px solid #e2e8f0; border-radius: 12px; padding: 20px; box-shadow: 0 4px 10px rgba(0,0,0,0.04);"><br />
<br />
[[文件:Protein_FGFR2_Structure_PDB.png|100px|FGFR2 激酶域结构 (PDB 2PZ5)]]<br />
</div><br />
<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">IV型受体酪氨酸激酶</div><br />
</div><br />
<br />
<table style="width: 100%; border-spacing: 0; border-collapse: collapse; font-size: 0.85em;"><br />
<tr><br />
<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>FGFR2</strong></td><br />
</tr><br />
<tr><br />
<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">基因全名</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">Fibroblast Growth Factor Receptor 2</td><br />
</tr><br />
<tr><br />
<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;">BEK, KGFR, CD332, CFD1</td><br />
</tr><br />
<tr><br />
<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;">10q26.13</td><br />
</tr><br />
<tr><br />
<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;">2263</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;">3689</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;">176943</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;">P21802</td><br />
</tr><br />
<tr><br />
<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">蛋白类型</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">受体酪氨酸激酶 (RTK)</td><br />
</tr><br />
<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;">~92-145 kDa</td><br />
</tr><br />
</table><br />
</div><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;">分子机制：剪接决定命运</h2><br />
<br />
<p style="margin: 15px 0; text-align: justify;"><br />
FGFR2 的配体结合特异性完全取决于其胞外 Ig-III 结构域的<strong>可变剪接</strong>。<br />
<br>1. <strong>FGFR2b (上皮型)：</strong> 包含外显子 8。特异性结合间充质来源的 FGF（如 FGF7, FGF10）。这是上皮细胞接收间质信号的关键。<br />
<br>2. <strong>FGFR2c (间充质型)：</strong> 包含外显子 9。特异性结合上皮来源的 FGF。<br />
<br>在肿瘤中，FGFR2b 的<strong>扩增</strong>或与 BICC1 等基因发生的<strong>融合</strong>，会导致配体非依赖性的二聚化或自分泌环路的形成，持续激活 RAS/MAPK 通路。<br />
</p><br />
<br />
<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：胆管癌与胃癌</h2><br />
<p style="margin: 15px 0; text-align: justify;"><br />
FGFR2 是肝内胆管癌（iCCA）最重要的治疗靶点，也是胃癌中潜在的重磅靶点。<br />
</p><br />
<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/疾病</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">变异形式</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">临床意义</th><br />
</tr><br />
<tr><br />
<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">肝内胆管癌 (iCCA)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>基因融合</strong> (~10-15%)<br>(如 FGFR2-BICC1/PPHLN1)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">年轻、女性、不吸烟患者中更常见。是 FGFR 抑制剂（佩米替尼、福巴替尼）的绝对适应症，疗效显著。</td><br />
</tr><br />
<tr><br />
<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">胃/胃食管结合部癌</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>基因扩增</strong> (~5-10%)<br>(多为 FGFR2b 亚型)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">与预后不良相关。由于多为 FGFR2b 过表达，单克隆抗体（Bemarituzumab）比小分子 TKI 更具潜力。</td><br />
</tr><br />
<tr><br />
<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">子宫内膜癌</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>激活性突变</strong> (~10-12%)<br>(S252W, N532K)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">常见于子宫内膜样腺癌。突变位点与颅缝早闭综合征的胚系突变位点高度重合（功能获得性）。</td><br />
</tr><br />
<tr><br />
<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">Apert/Crouzon 综合征</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>胚系突变</strong> (Germline)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">严重的常染色体显性遗传性骨骼发育疾病，表现为颅缝早闭、并指（趾）等畸形。</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：不可逆抑制剂与抗体</h2><br />
<p style="margin: 15px 0; text-align: justify;"><br />
针对 FGFR2 的治疗策略已从非选择性 TKI 进化到共价结合的不可逆抑制剂和亚型特异性抗体。<br />
</p><br />
<ul style="padding-left: 25px; color: #334155;"><br />
<li style="margin-bottom: 12px;"><strong>可逆性 ATP 竞争抑制剂：</strong><br />
<ul style="margin-top: 5px;"><br />
<li><strong>[[佩米替尼]] (Pemigatinib)：</strong> 首个获批用于 FGFR2 融合胆管癌的靶向药。FIGHT-202 研究显示 ORR 为 35.5%。</li><br />
<li><strong>[[英菲格拉替尼]] (Infigratinib)：</strong> 另一种高效口服抑制剂。</li><br />
</ul><br />
</li><br />
<li style="margin-bottom: 12px;"><strong>不可逆（共价）抑制剂：</strong> <strong>[[福巴替尼]] (Futibatinib)：</strong> 能够与 FGFR2 激酶域的半胱氨酸残基共价结合。对于某些对可逆性抑制剂产生耐药突变的患者仍有效。</li><br />
<li style="margin-bottom: 12px;"><strong>亚型特异性抗体：</strong> <strong>[[Bemarituzumab]]</strong> (FPA144)。特异性靶向 <strong>FGFR2b</strong> 亚型，通过阻断配体结合和增强 ADCC 效应杀伤肿瘤。FIGHT 试验显示其联合化疗在 FGFR2b+ 胃癌中显著延长生存期。</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>FGFR2-BICC1：</strong> 肝内胆管癌中最常见的融合形式，BICC1 提供二聚化结构域。</li><br />
<li style="margin-bottom: 12px;"><strong>Bemarituzumab：</strong> 首个靶向 FGFR2b 亚型的单克隆抗体，是胃癌精准治疗的希望。</li><br />
<li style="margin-bottom: 12px;"><strong>颅缝早闭 (Craniosynostosis)：</strong> FGFR2 功能获得性突变的典型表型，反映了其在骨骼发育中的核心作用。</li><br />
<li style="margin-bottom: 12px;"><strong>耐药突变：</strong> 类似 EGFR，FGFR2 也会产生“看门人”突变（如 V564F），阻碍药物结合。</li><br />
</ul><br />
<br />
<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 />
<br />
<p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"><br />
[1] <strong>Abou-Alfa GK, et al. (2020).</strong> <em>Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, single-arm, phase 2 study.</em> <strong>The Lancet Oncology</strong>. <br><br />
<span style="color: #475569;">[学术点评]：FIGHT-202 研究。具有里程碑意义，促成了佩米替尼作为首个 FGFR2 靶向药物获批，改变了胆管癌的治疗标准。</span><br />
</p><br />
<br />
<p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"><br />
[2] <strong>Goyal L, et al. (2023).</strong> <em>Futibatinib for FGFR2-Rearranged Intrahepatic Cholangiocarcinoma.</em> <strong>New England Journal of Medicine</strong>. <br><br />
<span style="color: #475569;">[学术点评]：FOENIX-CCA2 研究。证实了不可逆抑制剂福巴替尼在胆管癌中的显著疗效，尤其是对某些耐药突变的克服能力。</span><br />
</p><br />
<br />
<p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"><br />
[3] <strong>Arai Y, et al. (2014).</strong> <em>Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma.</em> <strong>Hepatology</strong>. <br><br />
<span style="color: #475569;">[学术点评]：首次通过 RNA 测序在胆管癌中鉴定出 FGFR2 融合基因，确立了其作为 iCCA 核心驱动事件的地位。</span><br />
</p><br />
<br />
<p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"><br />
[4] <strong>Wilkie AO, et al. (1995).</strong> <em>Apert syndrome results from localized mutations of FGFR2.</em> <strong>Nature Genetics</strong>. <br><br />
<span style="color: #475569;">[学术点评]：遗传学经典发现，将 Apert 综合征的病因锁定为 FGFR2 的特定错义突变，连接了发育生物学与临床遗传学。</span><br />
</p><br />
<br />
<p style="margin: 12px 0;"><br />
[5] <strong>Wainberg ZA, et al. (2022).</strong> <em>Efficacy and Safety of Bemarituzumab in Patients With FGFR2b-Selected Gastric or Gastroesophageal Junction Adenocarcinoma (FIGHT).</em> <strong>The Lancet Oncology</strong>. <br><br />
<span style="color: #475569;">[学术点评]：FIGHT 研究。展示了靶向 FGFR2b 的单抗 Bemarituzumab 联合化疗在胃癌一线治疗中的生存获益。</span><br />
</p><br />
</div><br />
<br />
<div style="margin: 40px 0; border: 1.5px solid #0f172a; border-radius: 8px; overflow: hidden; font-size: 0.95em;"><br />
<div style="background-color: #0f172a; color: #ffffff; text-align: center; font-weight: bold; padding: 10px; letter-spacing: 1px;">FGFR2 · 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 />
[[肝内胆管癌]] • [[Bemarituzumab]] • [[佩米替尼]] • [[胃癌]] • [[可变剪接]] • [[福巴替尼]] • [[Apert综合征]] • [[基因融合]]<br />
</div><br />
</div><br />
<br />
</div></div>
77921020