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FGFR4 - 版本历史
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">2026年1月1日 (四) 20:39的版本</td>
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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;"><div> <p style="font-size: 1.1em; margin: 10px 0; color: #334155; text-align: justify;"></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="font-size: 1.1em; margin: 10px 0; color: #334155; text-align: justify;"></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> <strong>FGFR4</strong>（Fibroblast Growth Factor Receptor 4）是 FGFR 家族的第四个成员，与该家族其他三个成员（FGFR1-3）在生物学功能上存在显著差异。FGFR4 主要在成熟的<strong>肝脏</strong>组织中高表达，它必须依赖共受体 <strong>[[β-Klotho]]</strong> (KLB) 才能高亲和力地结合内分泌型配体 <strong>[[FGF19]]</strong>。这一独特的 <strong>FGF19-KLB-FGFR4</strong> <del class="diffchange diffchange-inline">信号轴是调节肝脏胆汁酸合成（通过抑制 </del><strong>[[CYP7A1]]</strong>）和糖脂代谢的关键机制。在病理状态下，该信号轴的异常激活是驱动<strong>[[肝细胞癌]]</strong> (HCC) 发生发展的核心事件，约 30% 的 HCC 患者存在 FGF19 的扩增或过表达。此外，FGFR4 的激活性突变也是儿童<strong>[[横纹肌肉瘤]]</strong> (RMS) 的重要致病原因。</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> <strong>FGFR4</strong>（Fibroblast Growth Factor Receptor 4）是 <ins class="diffchange diffchange-inline"><strong>[[</ins>FGFR<ins class="diffchange diffchange-inline">]]</strong> </ins>家族的第四个成员，与该家族其他三个成员（FGFR1-3）在生物学功能上存在显著差异。FGFR4 主要在成熟的<strong><ins class="diffchange diffchange-inline">[[</ins>肝脏<ins class="diffchange diffchange-inline">]]</ins></strong>组织中高表达，它必须依赖共受体 <strong>[[β-Klotho]]</strong> (KLB) 才能高亲和力地结合内分泌型配体 <strong>[[FGF19]]</strong>。这一独特的 <strong>FGF19-KLB-FGFR4</strong> <ins class="diffchange diffchange-inline">信号轴是调节肝脏<strong>[[胆汁酸]]</strong>合成（通过抑制限速酶 </ins><strong>[[CYP7A1]]</strong>）和糖脂代谢的关键机制。在病理状态下，该信号轴的异常激活是驱动<strong>[[肝细胞癌]]</strong> (HCC) 发生发展的核心事件，约 30% 的 HCC 患者存在 FGF19 的扩增或过表达。此外，FGFR4 的激活性突变也是儿童<strong>[[横纹肌肉瘤]]</strong> (RMS) 的重要致病原因。</div></td></tr>
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<tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l61" >第61行：</td>
<td colspan="2" class="diff-lineno">第61行：</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> <tr></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> <tr></div></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> <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">相关肿瘤</th></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> <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">相关肿瘤</th></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> <td style="padding: 6px 12px; color: #0f172a;"><del class="diffchange diffchange-inline">肝癌 (HCC)</del>, 横纹肌肉瘤</td></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> <td style="padding: 6px 12px; color: #0f172a;"><ins class="diffchange diffchange-inline">[[肝细胞癌]]</ins>, <ins class="diffchange diffchange-inline">[[</ins>横纹肌肉瘤<ins class="diffchange diffchange-inline">]]</ins></td></div></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> </tr></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> </tr></div></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> </table></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> </table></div></td></tr>
<tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l79" >第79行：</td>
<td colspan="2" class="diff-lineno">第79行：</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> <br>激活的 FGFR4 信号进入细胞核，强力抑制 <strong>[[CYP7A1]]</strong>（胆固醇 7α-羟化酶）的转录。CYP7A1 是胆汁酸合成的限速酶。因此，FGFR4 的作用是负反馈调节，防止胆汁酸在肝脏内过度积聚导致毒性。</li></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> <br>激活的 FGFR4 信号进入细胞核，强力抑制 <strong>[[CYP7A1]]</strong>（胆固醇 7α-羟化酶）的转录。CYP7A1 是胆汁酸合成的限速酶。因此，FGFR4 的作用是负反馈调节，防止胆汁酸在肝脏内过度积聚导致毒性。</li></div></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> <li style="margin-bottom: 12px;"><strong>致癌信号：</strong></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> <li style="margin-bottom: 12px;"><strong>致癌信号：</strong></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> <br>在 HCC 中，当 FGF19 过量（通常由基因扩增引起）或 FGFR4 突变时，该信号轴不再仅限于代谢调节，而是持续激活 <strong>PI3K-AKT</strong> 和 <strong>STAT3</strong> 通路，驱动肝细胞的恶性增殖和抗凋亡。</li></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> <br>在 <ins class="diffchange diffchange-inline">[[肝细胞癌]] (</ins>HCC<ins class="diffchange diffchange-inline">) </ins>中，当 FGF19 过量（通常由基因扩增引起）或 FGFR4 突变时，该信号轴不再仅限于代谢调节，而是持续激活 <strong><ins class="diffchange diffchange-inline">[[</ins>PI3K-AKT<ins class="diffchange diffchange-inline">]]</ins></strong> 和 <strong><ins class="diffchange diffchange-inline">[[</ins>STAT3<ins class="diffchange diffchange-inline">]]</ins></strong> 通路，驱动肝细胞的恶性增殖和抗凋亡。</li></div></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> </ul></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> </ul></div></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> [[Image:FGF19_FGFR4_signaling_bile_acid_regulation.png|100px|FGF19-FGFR4 调节胆汁酸合成]]</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> [[Image:FGF19_FGFR4_signaling_bile_acid_regulation.png|100px|FGF19-FGFR4 调节胆汁酸合成]]</div></td></tr>
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2026-01-01T20:33:02Z
<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 />
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<strong>FGFR4</strong>（Fibroblast Growth Factor Receptor 4）是 FGFR 家族的第四个成员，与该家族其他三个成员（FGFR1-3）在生物学功能上存在显著差异。FGFR4 主要在成熟的<strong>肝脏</strong>组织中高表达，它必须依赖共受体 <strong>[[β-Klotho]]</strong> (KLB) 才能高亲和力地结合内分泌型配体 <strong>[[FGF19]]</strong>。这一独特的 <strong>FGF19-KLB-FGFR4</strong> 信号轴是调节肝脏胆汁酸合成（通过抑制 <strong>[[CYP7A1]]</strong>）和糖脂代谢的关键机制。在病理状态下，该信号轴的异常激活是驱动<strong>[[肝细胞癌]]</strong> (HCC) 发生发展的核心事件，约 30% 的 HCC 患者存在 FGF19 的扩增或过表达。此外，FGFR4 的激活性突变也是儿童<strong>[[横纹肌肉瘤]]</strong> (RMS) 的重要致病原因。<br />
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<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 />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">FGFR4</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Liver Metabolic Regulator (点击展开)</div><br />
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[[Image:FGF19_FGFR4_Klotho_complex.png|100px|FGF19-FGFR4-βKlotho 复合物]]<br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">肝脏特异性 / 代谢调控</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%;">基因符号</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">FGFR4</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">蛋白别名</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">TKF, JTK2, CD334</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">染色体位置</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">5q35.2</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">Entrez Gene</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">2264</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 ID</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P22455</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">OMIM 编号</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">136352</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">氨基酸数</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #b91c1c;"><strong>802 aa</strong></td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">关键配体</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;"><strong>[[FGF19]]</strong> (内分泌型)</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">必需共受体</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;"><strong>[[β-Klotho]]</strong> (KLB)</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">相关肿瘤</th><br />
<td style="padding: 6px 12px; color: #0f172a;">肝癌 (HCC), 横纹肌肉瘤</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：肝脏的代谢开关</h2><br />
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FGFR4 的信号传导模式与其他 FGFR 成员截然不同，它主要参与代谢稳态而非骨骼发育。<br />
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<li style="margin-bottom: 12px;"><strong>FGF19-FGFR4-KLB 轴：</strong><br />
<br>进食后，肠道分泌 <strong>[[FGF19]]</strong> 进入门静脉循环到达肝脏。在肝脏表面，FGF19 必须借助跨膜蛋白 <strong>[[β-Klotho]]</strong> (KLB) 的辅助，才能稳定结合 FGFR4。这一三元复合物的形成激活下游的 RAS-RAF-MAPK 通路。</li><br />
<li style="margin-bottom: 12px;"><strong>抑制胆汁酸合成：</strong><br />
<br>激活的 FGFR4 信号进入细胞核，强力抑制 <strong>[[CYP7A1]]</strong>（胆固醇 7α-羟化酶）的转录。CYP7A1 是胆汁酸合成的限速酶。因此，FGFR4 的作用是负反馈调节，防止胆汁酸在肝脏内过度积聚导致毒性。</li><br />
<li style="margin-bottom: 12px;"><strong>致癌信号：</strong><br />
<br>在 HCC 中，当 FGF19 过量（通常由基因扩增引起）或 FGFR4 突变时，该信号轴不再仅限于代谢调节，而是持续激活 <strong>PI3K-AKT</strong> 和 <strong>STAT3</strong> 通路，驱动肝细胞的恶性增殖和抗凋亡。</li><br />
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[[Image:FGF19_FGFR4_signaling_bile_acid_regulation.png|100px|FGF19-FGFR4 调节胆汁酸合成]]<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;">临床景观：肝癌与肉瘤</h2><br />
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<h3 style="margin-top: 0; color: #1e40af; font-size: 1.1em;">肝细胞癌 (HCC) 的新靶点</h3><br />
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约 30% 的 HCC 患者表现为 FGF19-FGFR4 轴的异常激活。研究表明，FGFR4 高表达与 HCC 的更具侵袭性的表型、高甲胎蛋白 (AFP) 水平以及较差的预后相关。与 FGFR1-3 抑制剂常见的高磷血症副作用不同，特异性抑制 FGFR4 会导致 CYP7A1 活性升高，副作用主要是<strong>腹泻</strong>（胆汁酸合成过多引起）。<br />
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<th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">疾病类型</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 />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[肝细胞癌]] (HCC)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">FGF19 扩增 / FGFR4 过表达</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">FGF19 是 HCC 癌前病变的关键驱动因子。FGF19 的高血清水平可作为筛选 FGFR4 抑制剂获益人群的生物标志物。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[横纹肌肉瘤]] (RMS)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">激活性点突变 (TKD)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">在约 7-8% 的 RMS（主要是胚胎型）中发现激酶结构域 (TKD) 突变，如 <strong>V550E</strong>、<strong>N535K</strong>。这些突变导致受体自发活化，驱动肿瘤生长。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">多态性 G388R</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">胚系 SNP (rs351855)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">FGFR4跨膜区的 Gly388Arg 多态性。携带 <strong>Arg388</strong> 等位基因的患者在乳腺癌、前列腺癌等多种肿瘤中表现出更强的转移倾向和更差的预后。</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;">治疗策略：选择性抑制</h2><br />
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由于泛 FGFR 抑制剂（Pan-FGFRi）会导致严重的高磷血症（FGFR1 阻断效应），开发高选择性的 FGFR4 抑制剂是该领域的热点。<br />
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<li style="margin-bottom: 12px;"><strong>FGFR4 选择性抑制剂：</strong><br />
<br>药物如 <strong>[[Fisogatinib]]</strong> (BLU-554) 和 <strong>Roblitinib</strong> (FGF401)。它们通过与 FGFR4 激酶区独特的半胱氨酸 (Cys552) 形成共价键，实现高度特异性抑制，避免了脱靶毒性。</li><br />
<li style="margin-bottom: 12px;"><strong>耐药机制：</strong><br />
<br>长期使用共价抑制剂可能导致“守门人”突变（如 <strong>V550L/M</strong>）或铰链区突变，阻止药物结合，这与 EGFR T790M 耐药机制类似。</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>French DM, et al. (2012).</strong> <em>Targeting FGFR4 inhibits hepatocellular carcinoma in preclinical mouse models.</em> <strong>[[PLoS One]]</strong>. <br><br />
<span style="color: #475569;">[学术点评]：临床前验证。利用特异性抗体阻断 FGFR4，证明了其在 FGF19 过表达的 HCC 模型中的显著抗肿瘤活性，为临床开发奠定了基础。</span><br />
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[2] <strong>Kim RD, et al. (2019).</strong> <em>First-in-Human Phase I Study of Fisogatinib (BLU-554), a Highly Potent and Selective Covalent FGFR4 Inhibitor, in Patients with Advanced Hepatocellular Carcinoma.</em> <strong>[[Cancer Discovery]]</strong>. <br><br />
<span style="color: #475569;">[学术点评]：临床首秀。Fisogatinib 的 I 期临床数据，展示了其在 FGF19+ HCC 患者中的初步疗效（ORR 17%），且未观察到高磷血症，验证了选择性靶向 FGFR4 的安全性优势。</span><br />
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[3] <strong>Inagaki T, et al. (2005).</strong> <em>Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis.</em> <strong>[[Cell Metabolism]]</strong>. <br><br />
<span style="color: #475569;">[学术点评]：生理机制。揭示了 FGF15/19 作为肠-肝轴信号分子，通过 FGFR4 调节 CYP7A1 和胆汁酸稳态的分子机制。</span><br />
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[4] <strong>Taylor JG 6th, et al. (2009).</strong> <em>Identification of FGFR4-activating mutations in human rhabdomyosarcomas that promote metastasis and poor survival.</em> <strong>[[Journal of Clinical Investigation]] (JCI)</strong>. <br><br />
<span style="color: #475569;">[学术点评]：肉瘤发现。首次报道了横纹肌肉瘤中存在的 FGFR4 激酶域激活性突变，拓展了 FGFR4 在肝癌之外的肿瘤驱动作用。</span><br />
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FGFR4 · 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;">关键伙伴</td><br />
<td style="padding: 10px 15px; color: #334155;">[[FGF19]] • [[β-Klotho]] (KLB) • [[CYP7A1]] • [[胆汁酸]]</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;">相关肿瘤</td><br />
<td style="padding: 10px 15px; color: #334155;">[[肝细胞癌]] (HCC) • [[横纹肌肉瘤]] (RMS) • [[乳腺癌]] (G388R)</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;">靶向药物</td><br />
<td style="padding: 10px 15px; color: #334155;">[[Fisogatinib]] (BLU-554) • [[Roblitinib]] • [[H3B-6527]]</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;">对比家族</td><br />
<td style="padding: 10px 15px; color: #334155;">[[FGFR1]] • [[FGFR2]] • [[FGFR3]] • [[泛FGFR抑制剂]]</td><br />
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