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SOS1 抑制剂 - 版本历史
2026-04-08T13:33:20Z
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2026年4月8日 (三) 07:53 223.160.138.153
2026-04-08T07:53:27Z
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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4月8日 (三) 07:53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>SOS1 抑制剂</strong>（SOS1 Inhibitors）是一类靶向鸟苷酸交换因子 <strong>[[SOS1]]</strong> 的新型抗肿瘤药物。SOS1 负责催化 <strong>[[KRAS]]</strong> 等 Ras 家族蛋白从非活性（GDP 结合）状态向活性（GTP 结合）状态转换。在携带 KRAS 突变或上游受体过度激活的肿瘤中，SOS1 抑制剂通过阻断这一关键的交换环节，能够有效抑制下游 <strong>[[MAPK]]</strong> <del class="diffchange diffchange-inline">通路的信号传递。截至 2026 年，SOS1 抑制剂在临床应用中的核心价值主要体现为“垂直抑制”策略，即通过与 </del>KRAS G12C 抑制剂或 MEK <del class="diffchange diffchange-inline">抑制剂联用，克服肿瘤的反馈性激活及获得性耐药，是攻克“不可成药”Ras </del>通路的重要前沿。</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>SOS1 抑制剂</strong>（SOS1 Inhibitors）是一类靶向鸟苷酸交换因子 <strong>[[SOS1]]</strong> 的新型抗肿瘤药物。SOS1 负责催化 <strong>[[KRAS]]</strong> 等 Ras 家族蛋白从非活性（GDP 结合）状态向活性（GTP 结合）状态转换。在携带 KRAS 突变或上游受体过度激活的肿瘤中，SOS1 抑制剂通过阻断这一关键的交换环节，能够有效抑制下游 <strong>[[MAPK]]</strong> <ins class="diffchange diffchange-inline">通路的信号传递。临床应用的核心价值主要体现为“垂直抑制”策略，即通过与 </ins>KRAS G12C 抑制剂或 MEK <ins class="diffchange diffchange-inline">抑制剂联用，克服肿瘤的反馈性激活及获得性耐药，是攻克 Ras </ins>通路的重要前沿。</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 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> <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：SOS1 抑制剂研发阵列 <del class="diffchange diffchange-inline">(截至 2026.04)</del></h2></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> <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：SOS1 抑制剂研发阵列</h2></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;"><div> <th style="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">药物名称</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="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">药物名称</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: 10px; border: 1px solid #cbd5e1; color: #475569;"><del class="diffchange diffchange-inline">研发公司</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: 10px; border: 1px solid #cbd5e1; color: #475569;"><ins class="diffchange diffchange-inline">研发状态</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: 10px; border: 1px solid #cbd5e1; color: #1e40af;"><del class="diffchange diffchange-inline">临床状态与关键动态</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: 10px; border: 1px solid #cbd5e1; color: #1e40af;"><ins class="diffchange diffchange-inline">临床意义与组合</ins></th></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;"><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: 8px; border: 1px solid #cbd5e1; font-weight: 600;">BI 1701963</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: 8px; border: 1px solid #cbd5e1; font-weight: 600;">BI 1701963</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: 8px; border: 1px solid #cbd5e1;"><del class="diffchange diffchange-inline">勃林格殷格翰</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: 8px; border: 1px solid #cbd5e1;"><ins class="diffchange diffchange-inline">临床 II 期</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: 8px; border: 1px solid #cbd5e1;"><del class="diffchange diffchange-inline">II 期临床进行中；与阿达格拉西布联用显示出良好的协同效力。</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: 8px; border: 1px solid #cbd5e1;"><ins class="diffchange diffchange-inline">与阿达格拉西布（Adagrasib）联用显示出良好的协同效力。</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: 8px; border: 1px solid #cbd5e1; font-weight: 600;"><del class="diffchange diffchange-inline">MRTX0902</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: 8px; border: 1px solid #cbd5e1; font-weight: 600;"><ins class="diffchange diffchange-inline">HM101207</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: 8px; border: 1px solid #cbd5e1;"><del class="diffchange diffchange-inline">BMS / Mirati</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: 8px; border: 1px solid #cbd5e1;"><ins class="diffchange diffchange-inline">IND 申报中</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: 8px; border: 1px solid #cbd5e1<del class="diffchange diffchange-inline">; color: #64748b</del>;"><del class="diffchange diffchange-inline"><strong>已终止</strong>（2026 年 2 月因商业战略调整停止研发）。</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: 8px; border: 1px solid #cbd5e1;"><ins class="diffchange diffchange-inline">新型高选择性抑制剂，旨在改善跨突变谱的抗肿瘤活性。</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: 8px; border: 1px solid #cbd5e1; font-weight: 600;"><del class="diffchange diffchange-inline">HM101207</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: 8px; border: 1px solid #cbd5e1; font-weight: 600;"><ins class="diffchange diffchange-inline">MRTX0902</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: 8px; border: 1px solid #cbd5e1;"><del class="diffchange diffchange-inline">韩美制药</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: 8px; border: 1px solid #cbd5e1;"><ins class="diffchange diffchange-inline">临床 I 期（已终止）</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: 8px; border: 1px solid #cbd5e1;"><del class="diffchange diffchange-inline">AACR 2026 发布最新进展：有效克服 KRAS 抑制剂诱导的缺氧存活机制。</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: 8px; border: 1px solid #cbd5e1;"><ins class="diffchange diffchange-inline">初步探索阶段。</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="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: 8px; border: 1px solid #cbd5e1; font-weight: 600;">VIC-SOS1-271</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: 8px; border: 1px solid #cbd5e1; font-weight: 600;">VIC-SOS1-271</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: 8px; border: 1px solid #cbd5e1;"><del class="diffchange diffchange-inline">Vicore Pharma</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: 8px; border: 1px solid #cbd5e1;"><ins class="diffchange diffchange-inline">临床前</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: 8px; border: 1px solid #cbd5e1;"><del class="diffchange diffchange-inline">临床前阶段，探索在罕见 </del>Ras <del class="diffchange diffchange-inline">突变实体瘤中的应用。</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: 8px; border: 1px solid #cbd5e1;"><ins class="diffchange diffchange-inline">针对特定罕见 </ins>Ras <ins class="diffchange diffchange-inline">突变实体瘤。</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-l102" >第102行：</td>
<td colspan="2" class="diff-lineno">第102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> <li style="margin-bottom: 12px;"><strong>攻克 KRAS G12C 耐药：</strong>对于使用索托拉西布或阿达格拉西布后出现进展的患者，通过联用 SOS1 抑制剂，可同时阻断 Ras 蛋白的激活态（TKI 作用）和前驱活化态（SOS1i 作用），显著推迟耐药时间。</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> <li style="margin-bottom: 12px;"><strong>攻克 KRAS G12C 耐药：</strong>对于使用索托拉西布或阿达格拉西布后出现进展的患者，通过联用 SOS1 抑制剂，可同时阻断 Ras 蛋白的激活态（TKI 作用）和前驱活化态（SOS1i 作用），显著推迟耐药时间。</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>针对非 G12C 突变的探索：</strong>对于缺乏直接抑制剂的 KRAS G12D 或 G12V 突变，SOS1 抑制剂作为通路调节剂，联用 MEK 抑制剂或 SHP2 抑制剂，为这部分患者提供了新的治疗可能性。</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> <li style="margin-bottom: 12px;"><strong>针对非 G12C 突变的探索：</strong>对于缺乏直接抑制剂的 KRAS G12D 或 G12V 突变，SOS1 抑制剂作为通路调节剂，联用 MEK 抑制剂或 SHP2 抑制剂，为这部分患者提供了新的治疗可能性。</li></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> <li style="margin-bottom: 12px;"><strong>精准分层：</strong><del class="diffchange diffchange-inline">2026 年的前沿研究建议，通过监测血浆 </del><strong>[[ctDNA]]</strong> 的动态变化来识别耐药克隆是否由 RTK-SOS1 旁路驱动，从而精准启动联合方案。</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> <li style="margin-bottom: 12px;"><strong>精准分层：</strong><ins class="diffchange diffchange-inline">前沿研究建议通过监测血浆 </ins><strong>[[ctDNA]]</strong> 的动态变化来识别耐药克隆是否由 RTK-SOS1 旁路驱动，从而精准启动联合方案。</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-l121" >第121行：</td>
<td colspan="2" class="diff-lineno">第121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></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></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> [1] <strong>Hofmann MH, et al. (<del class="diffchange diffchange-inline">2024/2026 Updated</del>).</strong> <em><del class="diffchange diffchange-inline">SOS1 inhibitor </del>BI 3406 <del class="diffchange diffchange-inline">shows in vivo antitumor activity </del>and <del class="diffchange diffchange-inline">synergizes </del>with <del class="diffchange diffchange-inline">KRASG12D inhibitors</del>.</em> <strong>[[<del class="diffchange diffchange-inline">PNAS</del>]]</strong>. <del class="diffchange diffchange-inline">121</del>(<del class="diffchange diffchange-inline">11</del>):<del class="diffchange diffchange-inline">e2422943122</del>.<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> [1] <strong>Hofmann MH, et al. (<ins class="diffchange diffchange-inline">2021</ins>).</strong> <em>BI<ins class="diffchange diffchange-inline">-</ins>3406<ins class="diffchange diffchange-inline">, a Potent </ins>and <ins class="diffchange diffchange-inline">Selective SOS1:pan-KRAS Inhibitor, Synergizes </ins>with <ins class="diffchange diffchange-inline">KRASG12C Inhibitors to Overcome Adaptive Resistance</ins>.</em> <strong>[[<ins class="diffchange diffchange-inline">Cancer Discovery</ins>]]</strong>. <ins class="diffchange diffchange-inline">11</ins>(<ins class="diffchange diffchange-inline">1</ins>):<ins class="diffchange diffchange-inline">142-157</ins>. <ins class="diffchange diffchange-inline">[Academic Review]</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;">[权威点评]<del class="diffchange diffchange-inline">：该研究确立了 </del>SOS1 作为 Ras 依赖型癌症干预靶点的价值，并展示了其在全谱 KRAS 突变中的联合潜力。</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;">[权威点评]<ins class="diffchange diffchange-inline">：该项研究奠定了 </ins>SOS1 作为 Ras 依赖型癌症干预靶点的价值，并展示了其在全谱 KRAS 突变中的联合潜力。</span></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;"></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> [2] <strong><del class="diffchange diffchange-inline">AACR 2026</del>.</strong> <em><del class="diffchange diffchange-inline">Abstract #3413: Targeting </del>KRAS<del class="diffchange diffchange-inline">-SOS1 to disarm hypoxic survival in lung adenocarcinoma</del>.</em><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> [2] <strong><ins class="diffchange diffchange-inline">Singhal A, et al. (2024)</ins>.</strong> <em><ins class="diffchange diffchange-inline">Mechanisms of resistance to </ins>KRAS <ins class="diffchange diffchange-inline">inhibitors and emerging therapeutic strategies</ins>.</em> <ins class="diffchange diffchange-inline"><strong>[[Nature Medicine]]</strong>. 30:969–983.</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;">[核心价值]<del class="diffchange diffchange-inline">：揭示了 </del>SOS1 <del class="diffchange diffchange-inline">抑制剂在缺氧微环境下增强 KRAS 靶向药疗效的新机制。</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;">[核心价值]<ins class="diffchange diffchange-inline">：详尽分析了包括 </ins>SOS1 <ins class="diffchange diffchange-inline">抑制在内的垂直抑制策略在克服 Ras 通路反馈耐药中的核心作用。</ins></span></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;"></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><del class="diffchange diffchange-inline">Nature Reviews Clinical Oncology</del>. (2025).</strong> <em><del class="diffchange diffchange-inline">Systematic and precise interventions for KRAS</del>-<del class="diffchange diffchange-inline">mutant cancers: The role of GEF inhibitors</del>.</em><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><ins class="diffchange diffchange-inline">Byun J, et al</ins>. (2025).</strong> <em><ins class="diffchange diffchange-inline">Discovery of a Novel SOS1</ins>-<ins class="diffchange diffchange-inline">KRASmulti Inhibitor, HM101207, Demonstrates a Broad-Spectrum Antitumor Activity</ins>.</em> <ins class="diffchange diffchange-inline"><strong>[[AACR Poster]]</strong>.</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;">[临床关联]<del class="diffchange diffchange-inline">：综述了包括 </del>SOS1 <del class="diffchange diffchange-inline">抑制剂在内的多模式精准疗法在克服 Ras 通路耐药中的核心作用。</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;">[临床关联]<ins class="diffchange diffchange-inline">：展示了新一代 </ins>SOS1 <ins class="diffchange diffchange-inline">抑制剂在缺氧微环境下增强靶向药效能的新机制及临床前进展。</ins></span></div></td></tr>
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223.160.138.153
https://www.yiliao.com/index.php?title=SOS1_%E6%8A%91%E5%88%B6%E5%89%82&diff=317684&oldid=prev
223.160.138.153：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
2026-04-08T07:49:35Z
<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>SOS1 抑制剂</strong>（SOS1 Inhibitors）是一类靶向鸟苷酸交换因子 <strong>[[SOS1]]</strong> 的新型抗肿瘤药物。SOS1 负责催化 <strong>[[KRAS]]</strong> 等 Ras 家族蛋白从非活性（GDP 结合）状态向活性（GTP 结合）状态转换。在携带 KRAS 突变或上游受体过度激活的肿瘤中，SOS1 抑制剂通过阻断这一关键的交换环节，能够有效抑制下游 <strong>[[MAPK]]</strong> 通路的信号传递。截至 2026 年，SOS1 抑制剂在临床应用中的核心价值主要体现为“垂直抑制”策略，即通过与 KRAS G12C 抑制剂或 MEK 抑制剂联用，克服肿瘤的反馈性激活及获得性耐药，是攻克“不可成药”Ras 通路的重要前沿。<br />
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<div style="font-size: 1.15em; font-weight: bold; letter-spacing: 1.2px;">SOS1 抑制剂</div><br />
<div style="font-size: 0.75em; opacity: 0.85; margin-top: 4px;">靶向 RAS-GEF 药物 · 点击展开</div><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">作用位点：Cdc25 催化口袋</div><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 45%;">靶点蛋白</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">SOS1 (Son of Sevenless 1)</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">Entrez ID</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">6654</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">HGNC ID</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">11187</td><br />
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<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">Q07889</td><br />
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<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">BI 1701963, HM101207</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569;">联用策略</th><br />
<td style="padding: 12px; color: #b91c1c;">KRAS(G12C) + SOS1i</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;">药理机制：阻断 Ras 通路的“总开关”</h2><br />
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SOS1 抑制剂并非直接靶向突变的 Ras 蛋白，而是通过干扰上游的激活机制来调节 Ras 的活性水平。其分子层面的作用路径如下：<br />
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[Image showing the role of SOS1 as a GEF in the RAS cycle and its inhibition blocking GTP binding]<br />
<ul style="padding-left: 25px; color: #334155;"><br />
<li style="margin-bottom: 12px;"><strong>催化阻断：</strong>SOS1 抑制剂结合在 SOS1 的 Cdc25 催化结构域上，阻止其与 KRAS-GDP 的结合。这导致 KRAS 无法完成从 GDP 向 GTP 的交换，使其被迫保持在非活性的“关闭”状态。</li><br />
<li style="margin-bottom: 12px;"><strong>反馈回路拦截：</strong>当肿瘤细胞受到 EGFR 或 KRAS 抑制剂打击时，常会产生代偿性的受体酪氨酸激酶（RTK）激活。SOS1 作为 RTK 与 Ras 之间的核心中继，其抑制剂能阻断这种反馈，使信号通路彻底哑火。</li><br />
<li style="margin-bottom: 12px;"><strong>泛 Ras 调节效应：</strong>由于 SOS1 是所有 Ras 异构体（KRAS、HRAS、NRAS）共用的鸟苷酸交换因子，抑制 SOS1 具有广谱调节 Ras 负荷的效果，有助于解决肿瘤内部的异质性问题。</li><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：SOS1 抑制剂研发阵列 (截至 2026.04)</h2><br />
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<th style="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">药物名称</th><br />
<th style="padding: 10px; border: 1px solid #cbd5e1; color: #475569;">研发公司</th><br />
<th style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">临床状态与关键动态</th><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1;">勃林格殷格翰</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">II 期临床进行中；与阿达格拉西布联用显示出良好的协同效力。</td><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1;">BMS / Mirati</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1; color: #64748b;"><strong>已终止</strong>（2026 年 2 月因商业战略调整停止研发）。</td><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">HM101207</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">韩美制药</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">AACR 2026 发布最新进展：有效克服 KRAS 抑制剂诱导的缺氧存活机制。</td><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">VIC-SOS1-271</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">Vicore Pharma</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">临床前阶段，探索在罕见 Ras 突变实体瘤中的应用。</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：垂直联合与耐药突围</h2><br />
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SOS1 抑制剂由于单药活性相对有限，目前的主要临床应用策略集中在“垂直抑制”模式：<br />
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<li style="margin-bottom: 12px;"><strong>攻克 KRAS G12C 耐药：</strong>对于使用索托拉西布或阿达格拉西布后出现进展的患者，通过联用 SOS1 抑制剂，可同时阻断 Ras 蛋白的激活态（TKI 作用）和前驱活化态（SOS1i 作用），显著推迟耐药时间。</li><br />
<li style="margin-bottom: 12px;"><strong>针对非 G12C 突变的探索：</strong>对于缺乏直接抑制剂的 KRAS G12D 或 G12V 突变，SOS1 抑制剂作为通路调节剂，联用 MEK 抑制剂或 SHP2 抑制剂，为这部分患者提供了新的治疗可能性。</li><br />
<li style="margin-bottom: 12px;"><strong>精准分层：</strong>2026 年的前沿研究建议，通过监测血浆 <strong>[[ctDNA]]</strong> 的动态变化来识别耐药克隆是否由 RTK-SOS1 旁路驱动，从而精准启动联合方案。</li><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;">关键相关概念</h2><br />
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<ul style="margin: 0; padding-left: 20px; color: #334155; list-style-type: none;"><br />
<li style="margin-bottom: 8px;"><strong>[[KRAS 抑制剂]]</strong>：SOS1 抑制剂的最佳“垂直打击”搭档。</li><br />
<li style="margin-bottom: 8px;"><strong>[[SHP2 抑制剂]]</strong>：位于 SOS1 更上游的调节靶点。</li><br />
<li style="margin-bottom: 8px;"><strong>[[GEF (鸟苷酸交换因子)]]</strong>：SOS1 所属的功能蛋白类别。</li><br />
<li style="margin-bottom: 8px;"><strong>[[反馈激活]]</strong>：靶向药物导致信号通路“死灰复燃”的生物学现象。</li><br />
<li style="margin-bottom: 8px;"><strong>[[努南综合征]]</strong>：SOS1 生殖系突变引起的经典遗传疾病。</li><br />
<li style="margin-bottom: 0;"><strong>[[Ras 周期]]</strong>：GDP 与 GTP 结合状态的动态平衡过程。</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>Hofmann MH, et al. (2024/2026 Updated).</strong> <em>SOS1 inhibitor BI 3406 shows in vivo antitumor activity and synergizes with KRASG12D inhibitors.</em> <strong>[[PNAS]]</strong>. 121(11):e2422943122.<br><br />
<span style="color: #475569;">[权威点评]：该研究确立了 SOS1 作为 Ras 依赖型癌症干预靶点的价值，并展示了其在全谱 KRAS 突变中的联合潜力。</span><br />
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[2] <strong>AACR 2026.</strong> <em>Abstract #3413: Targeting KRAS-SOS1 to disarm hypoxic survival in lung adenocarcinoma.</em><br><br />
<span style="color: #475569;">[核心价值]：揭示了 SOS1 抑制剂在缺氧微环境下增强 KRAS 靶向药疗效的新机制。</span><br />
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[3] <strong>Nature Reviews Clinical Oncology. (2025).</strong> <em>Systematic and precise interventions for KRAS-mutant cancers: The role of GEF inhibitors.</em><br><br />
<span style="color: #475569;">[临床关联]：综述了包括 SOS1 抑制剂在内的多模式精准疗法在克服 Ras 通路耐药中的核心作用。</span><br />
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<div style="background-color: #eff6ff; color: #1e40af; padding: 8px 15px; font-weight: bold; text-align: center; border-bottom: 1px solid #dbeafe;"><br />
Ras 信号通路精准调控 · 知识图谱<br />
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<td style="padding: 10px 15px; color: #334155;">[[KRAS]] • [[NRAS]] • [[HRAS]] • [[SHP2]] • [[EGFR]] • [[MAPK]]</td><br />
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<td style="padding: 10px 15px; color: #334155;">[[鸟苷酸交换]] • [[反馈激活拦截]] • [[垂直通路抑制]] • [[旁路耐药克服]]</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;">代表药物</td><br />
<td style="padding: 10px 15px; color: #334155;">[[BI 1701963]] • [[HM101207]] • [[Sotorasib]] • [[Adagrasib]]</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;">前沿方向</td><br />
<td style="padding: 10px 15px; color: #334155;">[[SOS1 PROTAC 降解剂]] • [[泛 Ras 抑制策略]] • 基于 ctDNA 的动态联合治疗</td><br />
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223.160.138.153