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ALK - 版本历史
2026-04-21T11:06:49Z
本wiki的该页面的版本历史
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https://www.yiliao.com/index.php?title=ALK&diff=315559&oldid=prev
2026年1月24日 (六) 12:54 77921020
2026-01-24T12:54:20Z
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">←上一版本</td>
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">2026年1月24日 (六) 12:54的版本</td>
</tr><tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l3" >第3行：</td>
<td colspan="2" class="diff-lineno">第3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> <div style="margin-bottom: 30px; border-bottom: 1.2px solid #e2e8f0; padding-bottom: 25px;"></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> <div style="margin-bottom: 30px; border-bottom: 1.2px solid #e2e8f0; padding-bottom: 25px;"></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> <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>ALK</strong>（Anaplastic Lymphoma Kinase），即<strong>间变性淋巴瘤激酶</strong>，属于<strong>[[胰岛素受体]]</strong>超家族的<strong>[[受体酪氨酸激酶]]</strong>（RTK）。在生理状态下，ALK 主要在胚胎期的神经系统发育中表达，成人组织中表达极低。然而，ALK 是著名的“多面手”原癌基因，主要通过<strong>[[染色体易位]]</strong>形成<strong>[[融合基因]]</strong>（Fusion Gene）来驱动癌症。最著名的例子是 2007 年在<strong>[[非小细胞肺癌]]</strong> (NSCLC) 中发现的 <strong>[[EML4-ALK]]</strong> 融合，这一发现将 ALK <del class="diffchange diffchange-inline">定义为肺癌的“钻石突变”（发生率低但疗效极好）。针对 </del>ALK 的靶向药物研发是精准医学的教科书级案例，目前已发展至第三代抑制剂（如<strong>[[洛拉替尼]]</strong>），显著改善了患者的生存期，尤其是在控制<strong>[[脑转移]]</strong>方面表现卓越。</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>ALK</strong>（Anaplastic Lymphoma Kinase），即<strong>间变性淋巴瘤激酶</strong>，属于<strong>[[胰岛素受体]]</strong>超家族的<strong>[[受体酪氨酸激酶]]</strong>（RTK）。在生理状态下，ALK 主要在胚胎期的神经系统发育中表达，成人组织中表达极低。然而，ALK 是著名的“多面手”原癌基因，主要通过<strong>[[染色体易位]]</strong>形成<strong>[[融合基因]]</strong>（Fusion Gene）来驱动癌症。最著名的例子是 2007 年在<strong>[[非小细胞肺癌]]</strong> (NSCLC) 中发现的 <strong>[[EML4-ALK]]</strong> 融合，这一发现将 ALK <ins class="diffchange diffchange-inline">定义为肺癌的“<strong>[[钻石突变]]</strong>”（发生率低但疗效极好）。针对 </ins>ALK 的靶向药物研发是精准医学的教科书级案例，目前已发展至第三代抑制剂（如<strong>[[洛拉替尼]]</strong>），显著改善了患者的生存期，尤其是在控制<strong>[[脑转移]]</strong>方面表现卓越。</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> </p></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></div></td></tr>
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<tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l19" >第19行：</td>
<td colspan="2" class="diff-lineno">第19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> [[Image:EML4_ALK_fusion_protein_structure.png|100px|EML4-ALK 融合蛋白结构]]</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:EML4_ALK_fusion_protein_structure.png|100px|EML4-ALK 融合蛋白结构]]</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> </div></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> </div></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> <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;"><del class="diffchange diffchange-inline">肺癌“钻石突变”</del></div></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> <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;"><ins class="diffchange diffchange-inline">肺癌“[[钻石突变]]”</ins></div></div></td></tr>
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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 colspan="2" class="diff-lineno" id="mw-diff-left-l82" >第82行：</td>
<td colspan="2" class="diff-lineno">第82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> <table style="width: 100%; border-collapse: collapse; border: 1.2px solid #cbd5e1; font-size: 0.95em; text-align: left;"></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 style="width: 100%; border-collapse: collapse; border: 1.2px solid #cbd5e1; font-size: 0.95em; text-align: left;"></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 style="background-color: #f8fafc; border-bottom: 2px solid #0f172a;"></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 style="background-color: #f8fafc; border-bottom: 2px solid #0f172a;"></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> <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: <del class="diffchange diffchange-inline">20</del>%;"><del class="diffchange diffchange-inline">代系</del></th></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> <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: <ins class="diffchange diffchange-inline">25</ins>%;"><ins class="diffchange diffchange-inline">疾病类型</ins></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> <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569<del class="diffchange diffchange-inline">; width: 30%</del>;"><del class="diffchange diffchange-inline">代表药物</del></th></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> <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;"><ins class="diffchange diffchange-inline">变异形式</ins></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> <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af<del class="diffchange diffchange-inline">; width: 50%</del>;">临床特征</th></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> <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">临床特征</th></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> <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="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: 10px; border: 1px solid #cbd5e1; font-weight: 600;"><del class="diffchange diffchange-inline">第一代</del></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: 10px; border: 1px solid #cbd5e1; font-weight: 600;"><ins class="diffchange diffchange-inline">[[非小细胞肺癌]] (NSCLC)</ins></td></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: 10px; border: 1px solid #cbd5e1;"><strong><del class="diffchange diffchange-inline">[[克唑替尼]]</del></strong></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: 10px; border: 1px solid #cbd5e1;"><strong><ins class="diffchange diffchange-inline">EML4-ALK</ins></strong> <ins class="diffchange diffchange-inline">融合 (3-7%)</ins></td></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: 10px; border: 1px solid #cbd5e1;"><del class="diffchange diffchange-inline">开创者。但</del><strong><del class="diffchange diffchange-inline">入脑能力差</del></strong><del class="diffchange diffchange-inline">，且易在 1 年左右耐药。</del></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: 10px; border: 1px solid #cbd5e1;"><ins class="diffchange diffchange-inline">被称为“<strong>[[钻石突变]]</strong>”。多见于<strong>年轻</strong>、<strong>从不吸烟</strong>或轻度吸烟的<strong>[[肺腺癌]]</strong>患者。容易发生</ins><strong><ins class="diffchange diffchange-inline">[[脑转移]]</ins></strong><ins class="diffchange diffchange-inline">。检测金标准为 [[FISH]] 或 [[IHC]] (Ventana D5F3)。</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> <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="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: 10px; border: 1px solid #cbd5e1; font-weight: 600;"><del class="diffchange diffchange-inline">第二代</del></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: 10px; border: 1px solid #cbd5e1; font-weight: 600;"><ins class="diffchange diffchange-inline">[[间变性大细胞淋巴瘤]] (ALCL)</ins></td></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: 10px; border: 1px solid #cbd5e1;"><strong><del class="diffchange diffchange-inline">[[阿来替尼]]</del></strong><del class="diffchange diffchange-inline"><br>[[恩沙替尼]] </del>(<del class="diffchange diffchange-inline">国产</del>)<del class="diffchange diffchange-inline"><br>[[布格替尼]]</del></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: 10px; border: 1px solid #cbd5e1;"><strong><ins class="diffchange diffchange-inline">NPM-ALK</ins></strong> <ins class="diffchange diffchange-inline">融合 (t</ins>(<ins class="diffchange diffchange-inline">2;5)</ins>)</td></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: 10px; border: 1px solid #cbd5e1;"><del class="diffchange diffchange-inline"><strong>一线标准 (SoC)</strong>。高入脑，mPFS > 34 个月，大幅降低脑转移风险。</del></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: 10px; border: 1px solid #cbd5e1;"><ins class="diffchange diffchange-inline">ALK 阳性 ALCL 预后通常优于 ALK 阴性患者。多见于儿童和年轻人。ALK 抑制剂在复发难治病例中有效。</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> <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="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: 10px; border: 1px solid #cbd5e1; font-weight: 600;"><del class="diffchange diffchange-inline">第三代</del></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: 10px; border: 1px solid #cbd5e1; font-weight: 600;"><ins class="diffchange diffchange-inline">[[神经母细胞瘤]]</td></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> <td style="padding: 10px; border: 1px solid #cbd5e1;"><<del class="diffchange diffchange-inline">strong</del>>[[<del class="diffchange diffchange-inline">洛拉替尼</del>]]<del class="diffchange diffchange-inline"></strong></del></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><ins class="diffchange diffchange-inline"> <td style="padding: 10px; border: 1px solid #cbd5e1;">F1174L, R1275Q 突变</ins></td></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: 10px; border: 1px solid #cbd5e1;"><<del class="diffchange diffchange-inline">strong</del>><del class="diffchange diffchange-inline">终结者</del><<del class="diffchange diffchange-inline">/strong</del>><del class="diffchange diffchange-inline">。克服 [[G1202R]] 等难治突变，CROWN 研究显示 5 年 PFS 率高达 60</del>%<del class="diffchange diffchange-inline">。</del></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: 10px; border: 1px solid #cbd5e1;"><ins class="diffchange diffchange-inline">约 10-15% 的高危神经母细胞瘤存在 ALK 突变或扩增，是重要的预后不良因子和潜在治疗靶点。</td></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"> </tr></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"> </ins><<ins class="diffchange diffchange-inline">tr></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"> <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;"</ins>>[[<ins class="diffchange diffchange-inline">炎性肌纤维母细胞瘤</ins>]] <ins class="diffchange diffchange-inline">(IMT)</ins></td></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> <td style="padding: 10px; border: 1px solid #cbd5e1;"><ins class="diffchange diffchange-inline">多种 ALK 融合</ins><<ins class="diffchange diffchange-inline">/td</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"> </ins><<ins class="diffchange diffchange-inline">td style="padding: 10px; border: 1px solid #cbd5e1;"</ins>><ins class="diffchange diffchange-inline">约 50</ins>% <ins class="diffchange diffchange-inline">的 IMT 携带 ALK 重排，对 ALK 抑制剂反应良好。</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>
</table>
77921020
https://www.yiliao.com/index.php?title=ALK&diff=315558&oldid=prev
2026年1月24日 (六) 12:52 77921020
2026-01-24T12:52:02Z
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">←上一版本</td>
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">2026年1月24日 (六) 12:52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> <div style="margin-bottom: 30px; border-bottom: 1.2px solid #e2e8f0; padding-bottom: 25px;"></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> <div style="margin-bottom: 30px; border-bottom: 1.2px solid #e2e8f0; padding-bottom: 25px;"></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> <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>ALK</strong>（Anaplastic Lymphoma Kinase），即<strong>间变性淋巴瘤激酶</strong>，属于[[胰岛素受体]]<del class="diffchange diffchange-inline">超家族的受体酪氨酸激酶（RTK）。在生理状态下，ALK </del>主要在胚胎期的神经系统发育中表达，成人组织中表达极低。然而，ALK 是著名的“多面手”原癌基因，主要通过<strong>[[染色体易位]]</strong><del class="diffchange diffchange-inline">形成融合基因（Fusion </del>Gene）来驱动癌症。最著名的例子是 2007 年在<strong>[[非小细胞肺癌]]</strong> (NSCLC) 中发现的 <strong>[[EML4-ALK]]</strong> 融合，这一发现将 ALK 定义为肺癌的“钻石突变”（发生率低但疗效极好）。针对 ALK 的靶向药物研发是精准医学的教科书级案例，目前已发展至第三代抑制剂（如<strong>[[洛拉替尼]]</strong>），显著改善了患者的生存期，尤其是在控制<strong>[[脑转移]]</strong>方面表现卓越。</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>ALK</strong>（Anaplastic Lymphoma Kinase），即<strong>间变性淋巴瘤激酶</strong>，属于<ins class="diffchange diffchange-inline"><strong></ins>[[胰岛素受体]]<ins class="diffchange diffchange-inline"></strong>超家族的<strong>[[受体酪氨酸激酶]]</strong>（RTK）。在生理状态下，ALK </ins>主要在胚胎期的神经系统发育中表达，成人组织中表达极低。然而，ALK 是著名的“多面手”原癌基因，主要通过<strong>[[染色体易位]]</strong><ins class="diffchange diffchange-inline">形成<strong>[[融合基因]]</strong>（Fusion </ins>Gene）来驱动癌症。最著名的例子是 2007 年在<strong>[[非小细胞肺癌]]</strong> (NSCLC) 中发现的 <strong>[[EML4-ALK]]</strong> 融合，这一发现将 ALK 定义为肺癌的“钻石突变”（发生率低但疗效极好）。针对 ALK 的靶向药物研发是精准医学的教科书级案例，目前已发展至第三代抑制剂（如<strong>[[洛拉替尼]]</strong>），显著改善了患者的生存期，尤其是在控制<strong>[[脑转移]]</strong>方面表现卓越。</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> </p></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></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> </div></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> </div></div></td></tr>
<tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l45" >第45行：</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> <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">检测金标准</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; border-bottom: 1px solid #e2e8f0;">检测金标准</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; border-bottom: 1px solid #e2e8f0; color: #0f172a;">[[Ventana-D5F3]] (IHC)<br>[[FISH]]</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; border-bottom: 1px solid #e2e8f0; color: #0f172a;"<ins class="diffchange diffchange-inline">><strong</ins>>[[Ventana-D5F3]]<ins class="diffchange diffchange-inline"></strong> </ins>(IHC)<br<ins class="diffchange diffchange-inline">><strong</ins>>[[FISH]]<ins class="diffchange diffchange-inline"></strong></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> <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 colspan="2" class="diff-lineno" id="mw-diff-left-l66" >第66行：</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> <br>1. <strong>启动子置换：</strong> ALK 受到 EML4 强启动子的驱动，在肺部细胞中异常高表达。</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>1. <strong>启动子置换：</strong> ALK 受到 EML4 强启动子的驱动，在肺部细胞中异常高表达。</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> <br>2. <strong>组成性二聚化：</strong> EML4 含有<strong>[[卷曲螺旋]]</strong> (Coiled-coil) 结构域，介导融合蛋白发生非配体依赖性的同源二聚化。</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>2. <strong>组成性二聚化：</strong> EML4 含有<strong>[[卷曲螺旋]]</strong> (Coiled-coil) 结构域，介导融合蛋白发生非配体依赖性的同源二聚化。</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>3. <strong>信号爆发：</strong> 二聚化导致 ALK 激酶域发生交叉[[自磷酸化]]，进而激活下游的 <strong>[[RAS]]/[[MAPK]]</strong>、<strong>[[PI3K]]/[[AKT]]</strong> 和 <strong>[[JAK]]/[[STAT]]</strong> 通路，驱动肿瘤恶性增殖。</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>3. <strong>信号爆发：</strong> 二聚化导致 ALK 激酶域发生交叉<ins class="diffchange diffchange-inline"><strong></ins>[[自磷酸化]]<ins class="diffchange diffchange-inline"></strong></ins>，进而激活下游的 <strong>[[RAS]]/[[MAPK]]</strong>、<strong>[[PI3K]]/[[AKT]]</strong> 和 <strong>[[JAK]]/[[STAT]]</strong> 通路，驱动肿瘤恶性增殖。</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>其他激活模式：</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>其他激活模式：</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[[神经母细胞瘤]]中，ALK 主要发生激酶结构域的<strong>点突变</strong>（如 F1174L, R1275Q）或基因扩增，同样导致激酶持续活化。</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"><strong></ins>[[神经母细胞瘤]]<ins class="diffchange diffchange-inline"></strong></ins>中，ALK 主要发生激酶结构域的<strong>点突变</strong>（如 F1174L, R1275Q）或基因扩增，同样导致激酶持续活化。</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;"></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 colspan="2" class="diff-lineno" id="mw-diff-left-l93" >第93行：</td>
<td colspan="2" class="diff-lineno">第93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> <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">第二代</td></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> <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">第二代</td></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: 10px; border: 1px solid #cbd5e1;"><strong>[[阿来替尼]]</strong><br>[[恩沙替尼]] (国产)</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: 10px; border: 1px solid #cbd5e1;"><strong>[[阿来替尼]]</strong><br>[[恩沙替尼]] (国产)<ins class="diffchange diffchange-inline"><br>[[布格替尼]]</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> <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>一线标准 (SoC)</strong>。高入脑，mPFS > 34 个月，大幅降低脑转移风险。</td></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> <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>一线标准 (SoC)</strong>。高入脑，mPFS > 34 个月，大幅降低脑转移风险。</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 colspan="2" class="diff-lineno" id="mw-diff-left-l118" >第118行：</td>
<td colspan="2" class="diff-lineno">第118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;"></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> [3] <strong>Solomon BJ, Bauer TM, De Marinis F, et al. (2024).</strong> <em>Lorlatinib Versus Crizotinib in Patients With Advanced ALK-Positive Non-Small-Cell Lung Cancer: 5-Year Outcomes From the CROWN Study.</em> <strong>[[Journal of Clinical Oncology]]</strong>. 2024.<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> [3] <strong>Solomon BJ, Bauer TM, De Marinis F, et al. (2024).</strong> <em>Lorlatinib Versus Crizotinib in Patients With Advanced ALK-Positive Non-Small-Cell Lung Cancer: 5-Year Outcomes From the CROWN Study.</em> <strong>[[Journal of Clinical Oncology]]</strong>. 2024<ins class="diffchange diffchange-inline">;42(10):1089-1099</ins>.<br></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;">[长期生存]：CROWN 研究的 5 年随访数据显示，洛拉替尼组的中位 PFS <del class="diffchange diffchange-inline">尚未达到，展示了三代药物惊人的持久控制力。</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> <span style="color: #475569;">[长期生存]：CROWN 研究的 5 年随访数据显示，洛拉替尼组的中位 PFS <ins class="diffchange diffchange-inline">尚未达到，5 年无进展生存率高达 60%，展示了三代药物惊人的持久控制力。</ins></span></div></td></tr>
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<div style="font-size: 1.25em; font-weight: bold; text-align: center; margin-bottom: 12px; color: #2c3e50;">ALK 基因 / 蛋白</div><br />
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<div style="background-color: #f9fafb; border: 1px solid #f3f4f6; border-radius: 8px; padding: 25px; text-align: center;"><br />
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<div style="font-size: 0.8em; color: #9ca3af; margin-top: 10px; font-weight: normal;">ALK 激酶结构域与融合模式图</div><br />
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<div class="mw-collapsible mw-collapsed"><br />
<div style="font-size: 0.9em; font-weight: bold; text-align: center; padding: 8px; color: #3b82f6; cursor: pointer;">📋 临床关键参数 (点击展开)</div><br />
<div class="mw-collapsible-content"><br />
{| style="width: 100%; font-size: 0.9em; border-spacing: 0; margin-top: 5px;"<br />
! style="text-align: left; padding: 8px 0; border-bottom: 1px solid #f3f4f6; color: #4b5563;" | 突变类型<br />
| style="padding: 8px 0; border-bottom: 1px solid #f3f4f6; font-weight: 600;" | 基因重排 (融合)<br />
|-<br />
! style="text-align: left; padding: 8px 0; border-bottom: 1px solid #f3f4f6; color: #4b5563;" | 优势癌种<br />
| style="padding: 8px 0; border-bottom: 1px solid #f3f4f6;" | NSCLC (3%-5%)<br />
|-<br />
! style="text-align: left; padding: 8px 0; border-bottom: 1px solid #f3f4f6; color: #4b5563;" | 检测标准<br />
| style="padding: 8px 0; border-bottom: 1px solid #f3f4f6;" | IHC (Ventana), FISH, NGS<br />
|-<br />
! style="text-align: left; padding: 8px 0; color: #4b5563;" | 药物代际<br />
| style="padding: 1, 2, 3 代 TKI"<br />
|}<br />
</div><br />
</div><br />
</div><br />
<br />
'''ALK'''（间变性淋巴瘤激酶，Anaplastic Lymphoma Kinase）是一种受体酪氨酸激酶。在生理状态下，ALK 在神经系统的发育中起作用，但在成人组织中表达极低。<br />
<br />
当 ALK 基因发生倒位或易位，与另一个基因（最常见的是 EML4）融合时，会产生具有持续激酶活性的融合蛋白，从而激活下游致癌信号通路（如 MAPK, PI3K/AKT, JAK/STAT）。由于这类患者对靶向药物反应极佳，ALK 融合常被临床医生称为“钻石突变”。<br />
<br />
== 分子机制 ==<br />
ALK 阳性肿瘤最主要的驱动形式是 **EML4-ALK** 融合。<br />
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<div style="text-align: center; margin: 25px 0; padding: 15px; background: #fafafa; border-radius: 6px; border-top: 1px solid #eee; border-bottom: 1px solid #eee;"><br />
<span style="font-family: 'Times New Roman', serif; font-size: 1.1em; font-weight: bold; color: #d93025;">EML4-ALK (Fusion)</span><br />
<span style="margin: 0 10px; color: #3b82f6; font-size: 1.3em;">→</span><br />
<span style="font-family: 'Times New Roman', serif; font-size: 1.1em; font-style: italic;">RAS / RAF / MEK / ERK</span><br />
<span style="margin: 0 8px; color: #94a3b8;">&</span><br />
<span style="font-family: 'Times New Roman', serif; font-size: 1.15em; font-style: italic;">JAK / STAT3</span><br />
</div><br />
<br />
== 检测技术对比：实话实说 ==<br />
临床上检测 ALK 融合的方法较多，每种技术都有其客观的“短板”。<br />
<br />
<center><br />
{| class="wikitable" style="width: 65%; text-align: center; margin: 20px 0; font-size: 0.9em; box-shadow: 0 2px 4px rgba(0,0,0,0.05);"<br />
|+ ALK 检测技术的客观评价<br />
|-<br />
! style="background: #f8f9fa;" | 检测方法 !! 优势 (Pros) !! 局限 (Cons)<br />
|-<br />
| '''IHC (免疫组化)''' || 速度快、便宜；Ventana D5F3 是筛查金标准 || 无法得知具体融合伴侣，存在假阳性可能<br />
|-<br />
| '''FISH (荧光原位杂交)''' || 经典的判读方法，不受融合伴侣限制 || 昂贵、对样本质量要求高，无法测突变<br />
|-<br />
| '''NGS (二代测序)''' || 可同时检测多个驱动基因及融合伴侣 || 周期长 (1-2周)；存在漏检部分复杂易位的风险<br />
|}<br />
</center><br />
<br />
== 靶向治疗与耐药现实 ==<br />
<br />
=== 1. 药物迭代 ===<br />
ALK 阳性患者的生存期由于 TKI 药物的迭代而显著延长：<br />
* '''一代 (克唑替尼)'''：开创了靶向时代，但入脑能力弱，易复发。<br />
* '''二代 (阿来替尼、布格替尼)'''：目前临床一线的主流选择，具有强大的脑转移控制能力。<br />
* '''三代 (洛拉替尼)'''：专门针对二代耐药设计，能覆盖绝大多数抗性突变（如 G1202R）。<br />
<br />
=== 2. 实话实说：耐药不可避免 ===<br />
尽管被称为“钻石突变”，但几乎所有患者最终都会面临耐药。<br />
* **耐药机制**：约 50% 的耐药由 ALK 激酶区的二次突变引起（如 G1202R, L1196M），另 50% 则是由于旁路激活（如 MET 扩增、HER2 突变）。<br />
* **临床现状**：一旦三代洛拉替尼耐药，目前的后续治疗方案往往仅剩化疗或参加临床试验，这是目前 ALK 治疗中的主要困境<ref>Lin JJ, et al. Mechanisms of Resistance to ALK Inhibitors: An Evolving Landscape. Microorganisms. 2020.</ref>。<br />
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== 参考文献 ==<br />
{{reflist}}<br />
<br />
<div style="clear: both; margin-top: 40px; border: 1px solid #a2a9b1; background-color: #f8f9fa; border-radius: 4px; overflow: hidden;"><br />
<div style="background-color: #dee2e6; text-align: center; font-weight: bold; padding: 6px; border-bottom: 1px solid #a2a9b1; color: #374151;">肺癌精准治疗与分子靶点</div><br />
{| style="width: 100%; background: transparent; border-spacing: 0; font-size: 0.9em;"<br />
|-<br />
! style="width: 15%; padding: 8px; background-color: #f1f5f9; text-align: right; border-bottom: 1px solid #fff;" | 驱动基因<br />
| style="padding: 8px; border-bottom: 1px solid #fff;" | [[EGFR]] • [[ALK]] • [[ROS1]] • [[RET]] • [[KRAS]] • [[MET]]<br />
|-<br />
! style="width: 15%; padding: 8px; background-color: #f1f5f9; text-align: right; border-bottom: 1px solid #fff;" | 代表药物<br />
| style="padding: 8px; border-bottom: 1px solid #fff;" | [[克唑替尼]] • [[阿来替尼]] • [[洛拉替尼]] • [[恩曲替尼]]<br />
|-<br />
! style="width: 15%; padding: 8px; background-color: #f1f5f9; text-align: right;" | 诊断技术<br />
| style="padding: 8px;" | [[IHC]] • [[FISH]] • [[NGS]] • [[液体活检]]<br />
|}<br />
</div><br />
<br />
[[Category:人类基因]]<br />
[[Category:肿瘤学]]<br />
[[Category:受体酪氨酸激酶]]</div>
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