查看“ROR1”的源代码

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            <strong>[[ROR1]]</strong>（<strong>[[Receptor Tyrosine Kinase Like Orphan Receptor 1]]</strong>）是一种典型的<strong>[[癌胚抗原]]</strong>（<strong>[[Oncofetal Antigen]]</strong>）。该[[蛋白质]]在胚胎发育阶段对[[神经系统]]、[[骨骼]]和[[血管]]的建成至关重要，但在出生后的正常[[组织]]中几乎不表达。然而，[[ROR1]]在多种恶性[[肿瘤]]（如[[慢性淋巴细胞白血病]]、[[三阴性乳腺癌]]、[[非小细胞肺癌]]等）中发生病理性的高表达，并作为<strong>[[非经典Wnt信号通路]]</strong>的受体促进肿瘤细胞的[[增殖]]、[[迁移]]和[[上皮-间质转化]]（[[EMT]]）。由于其在肿瘤与正常组织间极高的表达差异，[[ROR1]]已成为[[抗体偶联药物]]（[[ADC]]）、[[双特异性抗体]]及[[CAR-T]]细胞疗法开发的热门精准靶点。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">[[ROR1]]</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px;">[[Receptor Tyrosine Kinase]] · 点击展开详情</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">染色体定位：1p31.3</div>
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                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">4919</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[HGNC]]ID</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">10256</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[UniProt]]</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">Q01973</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[分子量]]</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">104.3kDa</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">信号配体</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[Wnt5a]]</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">相关领域</th>
                    <td style="padding: 12px; color: #0f172a;">[[ADC]] / [[CAR-T]]</td>
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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;">生物学机制：从胚胎导航到肿瘤驱动</h2>
    
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        [[ROR1]]作为一种受体[[酪氨酸激酶]]，在恶性转化中扮演着多重角色：
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        <li style="margin-bottom: 12px;"><strong>[[Wnt信号]]转导：</strong>[[ROR1]]主要通过结合配体[[Wnt5a]]激活[[非经典Wnt通路]]。该信号并不直接进入[[β-Catenin]]通路，而是通过激活[[RHO]]/[[RAC]]等[[GTP酶]]，重塑[[细胞骨架]]，增强肿瘤的[[侵袭性]]。</li>
        <li style="margin-bottom: 12px;"><strong>[[存活信号]]维持：</strong>在[[慢性淋巴细胞白血病]]（[[CLL]]）中，[[ROR1]]表达与[[PI3K/AKT]]通路的持续激活相关，通过抑制[[细胞凋亡]]程序，维持[[白血病]]克隆的[[存活]]。</li>
        <li style="margin-bottom: 12px;"><strong>诱导[[EMT]]过程：</strong>[[ROR1]]通过调控[[SNAIL]]、[[SLUG]]等转录因子，促进[[上皮细胞]]向[[间质细胞]]转化，这是肿瘤发生[[远处转移]]的关键步骤。</li>
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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;">核心药物研发管线</h2>

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                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">在研药物</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #475569;">药物类别</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">临床研究现状</th>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[Zilovertamab vedotin]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[ADC]] (MMAE载药)</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">针对[[淋巴瘤]]及[[NSCLC]]，由[[默沙东]]主导，处于临床后期阶段。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[DXC004A]] / [[DB-1301]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[ADC]] (喜树碱衍生物)</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[映恩生物]]开发，展现了良好的[[旁观者效应]]，处于全球[[多中心]]研究。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[Cirmtuzumab]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[单克隆抗体]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">首个进入临床的[[ROR1]]单抗，主要评估其在[[CLL]]中的安全性。</td>
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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：基于抗原密度的个体化选择</h2>
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        [[ROR1]]靶向治疗的成功高度依赖于对患者[[肿瘤]]组织中[[抗原]]密度的精准评估：
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        <li style="margin-bottom: 12px;"><strong>[[伴随诊断]]与IHC：</strong>应用[[ROR1-ADC]]前，需通过[[免疫组化]]（[[IHC]]）检测。由于正常组织不表达，只要[[肿瘤]]细胞呈现中/高强度表达，即被视为[[获益人群]]。</li>
        <li style="margin-bottom: 12px;"><strong>联合[[BTK抑制剂]]：</strong>在[[血液瘤]]治疗中，[[ROR1]]单抗联合[[伊布替尼]]等[[BTK抑制剂]]展现了协同效应，能更彻底地清除骨髓中的[[微小残留病灶]]（[[MRD]]）。</li>
        <li style="margin-bottom: 12px;"><strong>[[旁观者效应]]应用：</strong>对于[[ROR1]]表达具有[[异质性]]的实性肿瘤，优先选择携带膜通透性载药的新型[[ADC]]，以利用其[[旁观者效应]]覆盖阴性区域。</li>
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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>
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            <li style="margin-bottom: 8px;"><strong>[[Wnt5a]]：</strong>[[ROR1]]的主要功能[[配体]]，驱动肿瘤的定向迁移。</li>
            <li style="margin-bottom: 8px;"><strong>[[癌胚蛋白]]：</strong>具有典型的“[[开-关-开]]”表达模式，是[[免疫治疗]]极佳的脱靶保护靶点。</li>
            <li style="margin-bottom: 8px;"><strong>[[MMAE]] / [[P1021]]：</strong>[[ROR1-ADC]]中常用的[[细胞毒素]]载药，分别针对[[微管]]和[[DNA拓扑异构酶]]。</li>
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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>
        
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            [1] <strong>Kipps TJ. (2022).</strong> <em>ROR1: an oncofetal surface antigen with cancer-restricted expression and a role in tumor-cell survival and epithelial–mesenchymal transition.</em> <strong>[[Journal of Hematology & Oncology]]</strong>.[Academic Review]<br>
            <span style="color: #475569;">[权威点评]：该综述奠定了ROR1作为多癌种治疗通用靶点的理论基础。</span>
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            [2] <strong>Choi MY, et al. (2023).</strong> <em>Cirmtuzumab, a ROR1-Targeting Antibody, in Combination With Ibrutinib for Patients With CLL or Mantle Cell Lymphoma.</em> <strong>[[Cell Reports Medicine]]</strong>.<br>
            <span style="color: #475569;">[临床价值]：该临床研究证实了ROR1靶向联合方案在难治性血液瘤中的显著增效作用。</span>
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            [[ROR1]] 诊疗生态 · 知识图谱
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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;">关联配体</td>
                <td style="padding: 10px 15px; color: #334155;">[[Wnt5a]]•[[Wnt5b]]•[[ROR2]]•[[Frizzled]]</td>
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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;">治疗药物</td>
                <td style="padding: 10px 15px; color: #334155;">[[Zilovertamab]]•[[DXC004A]]•[[NBE-002]]•[[Cirmtuzumab]]</td>
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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;">研发实体</td>
                <td style="padding: 10px 15px; color: #334155;">[[默沙东]](MSD)•[[映恩生物]]•[[VelosBio]]•[[UCSD]]</td>
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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;">研究前沿</td>
                <td style="padding: 10px 15px; color: #334155;">[[针对ROR1的CAR-T临床安全评估]]•[[双抗引导的T细胞定向杀伤]]•[[基于ROR1的液体活检动态监测]]</td>
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