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胰腺癌是一种恶性程度极高的肿瘤，被认为是“癌中之王”。随着影像学检查水平的提高和针对遗传因素的早期检测，以及胰腺癌前病变的早期切除，其5年生存率从30年前的4%提高到13%。超过50%的胰腺癌患者发现时已经转移，因此提高对转移患者的治疗效果是亟待解决的难题。遗传因素和非遗传因素在肿瘤耐药机制中所发挥作用的真实比例暂不清楚。表观遗传机制在胰腺癌的发生和发展过程中逐渐被认为发挥关键作用，大量的证据表明肿瘤的遗传进化不可能代表唯一的，甚至最常见的耐药机制。非遗传因素实质上可能发挥更大的作用，如肿瘤表观遗传异质性。靶向蛋白降解嵌合体及表观遗传异常的“协同致死”治疗策略是胰腺癌治疗的最前沿领域，它是通过靶向决定细胞命运的基因调控网络而实现。深入解析胰腺癌的发病机制，明确肿瘤和微环境之间的相互作用，弄清其基因调控网络及其补偿通路之间的关系，有望突破传统理论的制约，创新性地发现高效、特异性的治疗策略，建立新的治疗模式和方法。
Abstract：Pancreatic cancer(PC) is a deadly disease with a poor prognosis. Over 50% of patients have been metastasized by the time of diagnosis. The five-year overall survival has been improved mainly by genomic markers and imaging surveillance in the past 30 years. The main issue of cancer recurrence is therapeutic resistance. The true prevalence of genetic and non-genetic mechanisms of resistance in cancer is largely unknown. The role of epigenetics is gradually realized to be the key of PC initiation and progression. The growing evidences demonstrate that genetic evolution is unlikely to represent the sole or even the most common mechanism of treatment resistance. Non-genetic factors may make more contributions substantially, including intratumor epigenetic heterogeneity. Proteolytic targeting chimeras(PROTAC) and epigenetic based ″synthetic lethality″ represent the promising of PC therapeutics by targeting cell fate determining regulation signaling network. Therefore, it is critical to understand the mechanism of pancreatic cancer initiation and progression, dissect the interaction of cancer cells and their microenvironment, clarify gene regulation network and the compensation mechanism of key components for signal pathway regulation network. To make these efforts, it is hopeful to pursuit the theoretical breakthrough for developing novel, high efficiency and more specific therapeutic strategies, utmost to set up novel therapeutic models and techniques.
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基本信息:
DOI：
中图分类号:R735.9
引用信息:
[1]张美英,郭明洲.胰腺癌的防治现状及表观遗传研究进展[J].胃肠病学和肝病学杂志,2025,34(09):1265-1268.
基金信息:
国家重点研发计划(2020YFC2002705); 国家自然科学基金委员会资助项目(82272632,81672138,82403742); 北京市自然科学基金资助(7254313); 解放军总医院青年自主创新科学基金项目(22QNCZ027)