查看“转移性胰腺癌”的源代码

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            <strong>[[转移性胰腺癌]]</strong>（<strong>[[Metastatic Pancreatic Cancer]]</strong>）是指起源于[[胰腺]]（主要为[[导管腺癌]]，[[PDAC]]）且已扩散至远端器官（如[[肝脏]]、[[腹膜]]、[[肺]]或[[骨]]）的[[恶性肿瘤]]，对应[[AJCC]]分期中的<strong>[[IV期]]</strong>。该病以极高的[[分子异质性]]、致密的[[纤维间质]]及严重的[[免疫抑制]]为特征，由于早期症状隐匿，约50%的患者在确诊时已处于转移阶段。分子层面，转移的发生常伴随<strong>[[KRAS]]</strong>（>90%）、<strong>[[TP53]]</strong>、<strong>[[CDKN2A]]</strong>和<strong>[[SMAD4]]</strong>等核心[[驱动基因]]的级联突变。截至2026年，治疗模式已由传统化疗演进为基于[[基因组学]]画像的[[精准治疗]]，包括[[KRAS抑制剂]]、[[PARP抑制剂]]及新型[[ADC]]药物的临床应用。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">[[转移性胰腺癌]]</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px;">[[Metastatic PDAC]] · 点击展开详情</div>
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            <div style="padding: 25px; text-align: center; background-color: #f8fafc;">
                <div style="padding: 10px; border: 1px solid #e2e8f0; border-radius: 8px; background: #fff; display: inline-block;">
                    <div style="width: 140px; height: 90px; background-color: #f1f5f9; display: flex; align-items: center; justify-content: center; color: #94a3b8; font-size: 0.8em; padding: 10px; text-align: center;">[[胰腺癌]]远端转移路径图</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心驱动：[[KRAS]]突变</div>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 45%;">[[Entrez]]ID([[KRAS]])</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">3845</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([[KRAS]])</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">6407</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;">P01116</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">关键分子量</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">21kDa ([[p21-ras]])</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">主要[[标志物]]</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[CA19-9]]•[[CEA]]</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">[[ICD-10]]</th>
                    <td style="padding: 6px 12px; color: #0f172a;">C25.9 / C78.7</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;">分子机制：从原位浸润到远端种植</h2>
    
    <p style="margin: 15px 0; text-align: justify;">
        [[转移性胰腺癌]]的扩散是一个多步骤、受高度调控的[[生物学]]过程，涉及肿瘤细胞与[[微环境]]的复杂互作：
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    <ul style="padding-left: 25px; color: #334155;">
        <li style="margin-bottom: 12px;"><strong>[[上皮-间质转化]]（EMT）：</strong>受[[TGF-β]]及[[SMAD4]]信号缺失驱动，肿瘤细胞失去极性并获得[[运动能力]]，穿透[[基底膜]]进入血液循环。</li>
        <li style="margin-bottom: 12px;"><strong>[[纤维基质]]屏障与缺氧：</strong>胰腺癌特有的[[促纤维增生]]反应（[[Desmoplasia]]）导致局部[[组织压]]升高，限制药物渗透，同时诱导[[缺氧诱导因子]]（[[HIF-1α]]）激活，增强细胞的应激存活。</li>
        <li style="margin-bottom: 12px;"><strong>[[外泌体]]与预转移龛形成：</strong>原发灶通过释放含有[[特定核酸]]及[[蛋白质]]的[[外泌体]]，调节肝脏等靶器官的[[免疫环境]]，为癌细胞的着陆铺平道路。</li>
        <li style="margin-bottom: 12px;"><strong>[[代谢重编程]]：</strong>为了在远端贫瘠环境中生存，转移细胞通过[[自噬]]及[[谷氨酰胺]]代谢途径进行[[产能优化]]。</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;">2026年最新临床治疗方案矩阵</h2>

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                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">治疗阶段</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #475569;">推荐方案/药物</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">分层获益特征</th>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">一线标准[[化疗]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[FOLFIRINOX]] 或 [[AG方案]]（吉西他滨+白蛋白紫杉醇）</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">身体状况较好([[ECOG]] 0-1)患者的首选。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[维持治疗]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[奥拉帕利]] (Olaparib)</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">针对携带[[生殖系BRCA]]突变且一线含铂化疗稳定的患者。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">二线及以后</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[伊立替康脂质体]] / [[KRAS抑制剂]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">针对[[KRAS G12C]]或[[G12D]]突变患者的靶向突围。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[免疫探索]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[PD-1抑制剂]]+[[白蛋白紫杉醇]]+[[白介素]]类</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">旨在通过[[基质重塑]]增加肿瘤免疫浸润。</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;">诊疗策略：全病程管理与精准分层</h2>
    <p style="margin: 15px 0; text-align: justify;">
        转移性阶段的治疗目标已从单纯的“缓解”转向“质量与生存双优”：
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    <ul style="padding-left: 25px; color: #334155;">
        <li style="margin-bottom: 12px;"><strong>[[基因检测]]前置：</strong>所有转移性患者确诊后应立即行[[NGS大面板检测]]，识别[[BRCA]]、[[MSI-H]]、[[NTRK]]及[[KRAS]]亚型。</li>
        <li style="margin-bottom: 12px;"><strong>[[CA19-9]]动态监测：</strong>该标志物不仅用于诊断，其水平下降幅度（>50%）是预测化疗[[客观缓解率]]（[[ORR]]）的重要指标。</li>
        <li style="margin-bottom: 12px;"><strong>[[姑息治疗]]与疼痛管理：</strong>晚期常伴有严重的[[腹腔神经丛]]浸润。建议尽早介入[[腹腔神经节阻滞]]及[[阿片类药物]]梯级治疗。</li>
        <li style="margin-bottom: 12px;"><strong>[[胰酶替代治疗]]（PERT）：</strong>针对胰腺外分泌功能不全导致的[[营养不良]]及[[恶病质]]，改善晚期患者的生活质量及[[化疗耐受性]]。</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>[[KRAS G12D]]：</strong>胰腺癌中最常见的突变亚型，2026年已有多个高选择性降解剂进入[[临床试验]]。</li>
            <li style="margin-bottom: 8px;"><strong>[[液体活检]]：</strong>利用[[ctDNA]]监测晚期治疗过程中的[[克隆演变]]及早期的[[耐药]]迹象。</li>
            <li style="margin-bottom: 8px;"><strong>[[循环肿瘤细胞]]（CTC）：</strong>作为预测转移风险及评估[[化疗]]敏感性的活体证据。</li>
            <li style="margin-bottom: 8px;"><strong>[[合成致死]]：</strong>[[PARP抑制剂]]在[[HRD]]缺陷患者中发挥效力的核心遗传学机制。</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>
        
        <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;">
            [1] <strong>Conroy T, et al. (2011/2024 update).</strong> <em>FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer: Long-term follow-up from the PRODIGE study.</em> <strong>[[The New England Journal of Medicine]]</strong>.[Academic Review]<br>
            <span style="color: #475569;">[权威点评]：确立了三联方案在转移性阶段作为体健患者标准治疗的基石地位。</span>
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        <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;">
            [2] <strong>Golan T, et al. (2019/2025 update).</strong> <em>Maintenance Olaparib in Patients with Germline BRCA-Mutated Metastatic Pancreatic Cancer (POLO Trial).</em> <strong>[[The New England Journal of Medicine]]</strong>.<br>
            <span style="color: #475569;">[核心价值]：开启了胰腺癌“化疗减毒、靶向维持”的精准医学新时代。</span>
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            [[转移性胰腺癌]] 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;">驱动靶点</td>
                <td style="padding: 10px 15px; color: #334155;">[[KRAS]]•[[TP53]]•[[BRCA1/2]]•[[CDKN2A]]•[[SMAD4]]•[[c-MET]]</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;">治疗组合</td>
                <td style="padding: 10px 15px; color: #334155;">[[FOLFIRINOX]]•[[吉西他滨+白蛋白紫杉醇]]•[[PARP抑制剂]]•[[伊立替康脂质体]]</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;">战略实体</td>
                <td style="padding: 10px 15px; color: #334155;">[[NCCN]]•[[ASCO]]•[[CSCO]]•[[AstraZeneca]]•[[Gilead]]</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KRAS G12D的靶向降解剂研究]]•[[针对基质调节的ADC开发]]•[[个体化新抗原疫苗应用]]</td>
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