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大细胞神经内分泌癌（新） - 版本历史
2026-05-09T07:38:07Z
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2026年1月27日 (二) 10:30 77921020
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2026年1月27日 (二) 07:06 77921020
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2026年1月27日 (二) 07:04 77921020
2026-01-27T07:04:29Z
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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27日 (二) 07:04的版本</td>
</tr><tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l54" >第54行：</td>
<td colspan="2" class="diff-lineno">第54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> <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">氨基酸数</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;">氨基酸数</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> <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #b91c1c;"><strong>1210 aa</strong></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: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #b91c1c;"><strong>1210 aa</strong></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><ins style="font-weight: bold; text-decoration: none;"> </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 style="font-weight: bold; text-decoration: none;"> <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 style="font-weight: bold; text-decoration: none;"> <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">分子量</th></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 style="font-weight: bold; text-decoration: none;"> <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">~170 kDa (成熟糖基化)</td></ins></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>
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<td colspan="2" class="diff-lineno">第66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> <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">关键配体</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;">关键配体</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> <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[EGF]], [[TGF-α]]</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: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[EGF]], [[TGF-α]]</td></div></td></tr>
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<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 style="font-weight: bold; text-decoration: none;"> <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 style="font-weight: bold; text-decoration: none;"> <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">靶向药物</th></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 style="font-weight: bold; text-decoration: none;"> <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[奥希替尼]], [[吉非替尼]], [[西妥昔单抗]]</td></ins></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>
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77921020
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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
2026-01-27T06:58:26Z
<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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<p style="font-size: 1.1em; margin: 10px 0; color: #334155; text-align: justify;"><br />
<strong>EGFR</strong>（Epidermal Growth Factor Receptor，表皮生长因子受体），亦称为 <strong>ErbB1</strong> 或 <strong>HER1</strong>，是 ErbB 受体酪氨酸激酶家族的成员。作为细胞膜表面的重要“天线”，它在结合配体（如 <strong>[[EGF]]</strong>、TGF-α）后发生二聚化，激活下游的 <strong>[[MAPK/ERK]]</strong> 和 <strong>[[PI3K-AKT]]</strong> 信号通路，驱动细胞分裂和生存。EGFR 是肿瘤学历史上研究最深入的靶点之一，尤其是在 <strong>[[非小细胞肺癌]]</strong> (NSCLC) 中。EGFR 激酶结构域的敏感突变（如 <strong>19号外显子缺失</strong> 和 <strong>L858R</strong>）被定义为肺癌的“黄金突变”，它们不仅驱动肿瘤发生，还是各代 <strong>[[EGFR-TKI]]</strong>（如<strong>[[奥希替尼]]</strong>）的特异性靶标，彻底改变了肺腺癌的治疗格局。<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;">EGFR / ErbB1</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Receptor Tyrosine Kinase (点击展开)</div><br />
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<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 />
[Image:EGFR_dimerization_structure.png|100px|EGFR 二聚体结构]<br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">酪氨酸激酶 / 生长信号</div><br />
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<table style="width: 100%; border-spacing: 0; border-collapse: collapse; font-size: 0.85em;"><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;">EGFR</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">全称</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">Epidermal Growth Factor Receptor</td><br />
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<tr><br />
<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;">7p11.2</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;">1956</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;">P00533</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;">131550</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">酶类别</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">受体酪氨酸激酶 (RTK)</td><br />
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<tr><br />
<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>1210 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;">突变热点</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #b91c1c;"><strong>L858R</strong>, <strong>Exon 19 del</strong>, T790M</td><br />
</tr><br />
<tr><br />
<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;">[[EGF]], [[TGF-α]]</td><br />
</tr><br />
<tr><br />
<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">临床意义</th><br />
<td style="padding: 6px 12px; color: #b91c1c;">肺腺癌, 结直肠癌, 胶质母细胞瘤</td><br />
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</table><br />
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<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：激酶构象锁的破坏</h2><br />
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<p style="margin: 15px 0; text-align: justify;"><br />
EGFR 蛋白由胞外配体结合域、跨膜域和胞内激酶结构域组成。在野生型 EGFR 中，激酶结构域通常处于自抑制（Auto-inhibited）的闭合构象。致癌突变通过破坏这种抑制机制，导致受体在无配体情况下持续激活。<br />
</p><br />
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<ul style="padding-left: 25px; color: #334155;"><br />
<li style="margin-bottom: 12px;"><strong>敏感突变 (Sensitizing Mutations)：</strong><br />
<br>最常见的突变是 <strong>Exon 19 缺失 (19del)</strong> 和 <strong>L858R 点突变</strong>（Exon 21）。这些突变改变了 ATP 结合袋周围的结构，优先稳定了激酶的活性构象（Active Conformation），使其对 ATP 的亲和力略有下降，但对 <strong>[[EGFR-TKI]]</strong> 抑制剂的结合亲和力显著增加。</li><br />
<li style="margin-bottom: 12px;"><strong>守门人突变 (Gatekeeper Mutation)：</strong><br />
<br>代表突变是 <strong>T790M</strong>（Exon 20）。在长期使用一代 TKI 后，位于 ATP 结合口袋深处的 790 位苏氨酸突变为甲硫氨酸。体积较大的侧链产生了空间位阻，阻碍了一代药物的结合，同时恢复了对 ATP 的亲和力，导致耐药。</li><br />
</ul><br />
[Image:EGFR_signaling_cascade_mutations.png|100px|EGFR 突变与 TKI 结合示意图]<br />
<br />
<h2 style="background: #fff1f2; color: #9f1239; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #9f1239; font-weight: bold;">临床警示：肺癌精准治疗的基石</h2><br />
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<h3 style="margin-top: 0; color: #be123c; font-size: 1.1em;">亚裔与不吸烟人群的高发性</h3><br />
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在亚裔、女性、不吸烟的肺腺癌患者中，EGFR 突变率高达 <strong>40%-50%</strong>（西方人群仅为 10-15%）。<br />
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<strong>必检原则与脑转移：</strong><br><br />
所有晚期非鳞状 NSCLC 患者必须在初诊时检测 EGFR。鉴于 EGFR 阳性患者发生<strong>[[脑转移]]</strong>的风险较高，选择具有高血脑屏障透过率的第三代 TKI（如奥希替尼）已成为一线治疗的标准优选。<br />
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<th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">疾病</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">突变特征</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">临床意义 / 治疗</th><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[非小细胞肺癌]] (经典型)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">Exon 19 del, L858R</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">一线首选 <strong>[[奥希替尼]]</strong> (Osimertinib)，PFS 显著优于化疗和一代 TKI。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[非小细胞肺癌]] (耐药型)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">T790M, C797S</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">T790M 可用奥希替尼挽救；C797S 是奥希替尼耐药的主要原因，目前尚无获批药物，需通过化疗或双抗解决。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[非小细胞肺癌]] (罕见型)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">Exon 20 插入 (20ins)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">对传统 TKI 不敏感。可用 <strong>[[埃万妥单抗]]</strong> (Amivantamab) 或小分子药物舒沃替尼。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[结直肠癌]] (CRC)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">过表达 / 扩增</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">仅在 RAS/BRAF 野生型时有效。使用单抗类药物 <strong>[[西妥昔单抗]]</strong> 或帕尼单抗。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[胶质母细胞瘤]] (GBM)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">EGFRvIII (缺失突变)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">虽然突变率高，但目前针对 EGFR 的靶向治疗在 GBM 中尚未取得确切的生存获益。</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;">治疗演进：从吉非替尼到奥希替尼</h2><br />
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EGFR 抑制剂的研发史就是人类对抗肿瘤耐药的进化史。<br />
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<li style="margin-bottom: 12px;"><strong>第一代 (可逆结合)：</strong><br />
<br><strong>[[吉非替尼]]</strong> (Gefitinib)、厄洛替尼。开启了肺癌靶向治疗时代（IPASS 研究），但患者通常在 10-14 个月后因 T790M 突变耐药。</li><br />
<li style="margin-bottom: 12px;"><strong>第二代 (不可逆结合)：</strong><br />
<br><strong>[[阿法替尼]]</strong> (Afatinib)、达可替尼。通过共价键结合泛 ErbB 受体，疗效略强但皮疹和腹泻副作用更重。</li><br />
<li style="margin-bottom: 12px;"><strong>第三代 (突变选择性)：</strong><br />
<br><strong>[[奥希替尼]]</strong> (Osimertinib)。专门设计用于克服 T790M 耐药，同时保留了对敏感突变的活性，且入脑能力极强。FLAURA 研究确立了其不可撼动的一线地位。</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>Lynch TJ, Bell DW, Sordella R, et al. (2004).</strong> <em>Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib.</em> <strong>[[New England Journal of Medicine]]</strong>. 2004;350(21):2129-2139.<br><br />
<span style="color: #475569;">[学术点评]：开山之作。哈佛团队首次揭示了 EGFR 激酶域突变与吉非替尼疗效之间的决定性关系，标志着肺癌精准医疗的诞生。</span><br />
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[2] <strong>Mok TS, Wu YL, Thongprasert S, et al. (2009).</strong> <em>Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.</em> <strong>[[New England Journal of Medicine]]</strong>. 2009;361(10):947-957.<br><br />
<span style="color: #475569;">[学术点评]：IPASS 研究。这是首个在全亚洲进行的重磅三期临床，由吴一龙教授等牵头，证实了在特定人群（不吸烟腺癌）中，靶向治疗优于传统化疗，确立了“先检测后治疗”的原则。</span><br />
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[3] <strong>Soria JC, Ohe Y, Vansteenkiste J, et al. (2018).</strong> <em>Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer.</em> <strong>[[New England Journal of Medicine]]</strong>. 2018;378(2):113-125.<br><br />
<span style="color: #475569;">[学术点评]：FLAURA 研究。证实了三代药物奥希替尼在一线治疗中相比一代药物显著延长了总生存期（OS）和无进展生存期（PFS），并表现出卓越的中枢神经系统控制力，改写了全球指南。</span><br />
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[4] <strong>Pao W, Miller V, Zakowski M, et al. (2005).</strong> <em>EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib.</em> <strong>[[Proceedings of the National Academy of Sciences]]</strong>. 2004;101(36):13306-13311.<br><br />
<span style="color: #475569;">[学术点评]：人群关联。进一步阐明了 EGFR 突变与临床特征（不吸烟、腺癌）的强关联性，为临床患者筛选提供了依据。</span><br />
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EGFR · 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;">家族成员</td><br />
<td style="padding: 10px 15px; color: #334155;">[[EGFR]] (ErbB1) • [[HER2]] (ErbB2) • [[HER3]] • [[HER4]]</td><br />
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<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">关键突变</td><br />
<td style="padding: 10px 15px; color: #334155;">[[19del]] • [[L858R]] • [[T790M]] (耐药) • [[C797S]] (三代耐药)</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;">上市药物</td><br />
<td style="padding: 10px 15px; color: #334155;">[[奥希替尼]] • [[吉非替尼]] • [[埃万妥单抗]] • [[西妥昔单抗]]</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;">副作用</td><br />
<td style="padding: 10px 15px; color: #334155;">[[皮疹]] (痤疮样) • [[腹泻]] • 甲沟炎 • 间质性肺炎</td><br />
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