Epigenetic treatment of pancreatic cancer: is there a therapeutic perspective on the horizon?
Epigenetic treatment of pancreatic cancer: is there a therapeutic perspective on the horizon?
复制标题
胰腺癌的表观遗传治疗：地平线上是否有治疗视角？
DOI：
10.1136/gutjnl-2016-312539
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发表时间：
2017-01
期刊：
影响因子：
24.5
通讯作者：
Ellenrieder V
中科院分区：
文献类型：
--
作者：
Hessmann E;Johnsen SA;Siveke JT;Ellenrieder V
胰腺导管腺癌(PDAC)是最具侵袭性的恶性肿瘤之一，5年生存率为7%。由于发病率上升、诊断延迟和治疗选择不足，PDAC预计很快就会成为癌症相关死亡的主要原因之一。虽然强化的细胞抑制联合治疗，特别是吉西他滨联合NAB-紫杉醇和亚叶酸、氟尿嘧啶、伊立替康、奥沙利铂(FOLFIRINOX)方案，在疗效和存活率方面比单独使用吉西他滨提供了一些改善，但在治疗转移性胰腺癌方面的突破仍然遥不可及。然而，最近的翻译研究活动表明，无论是免疫反应的调节，还是表观遗传修饰的药理学靶向，或者与化疗相结合，都可能为包括胰腺癌在内的胃肠道癌症实体开辟非常强大的治疗途径。关键的表观遗传因子和染色质修饰蛋白的去调控，特别是那些负责添加、移除或识别翻译后组蛋白修饰的蛋白，经常在人类胰腺癌中发现，因此构成了特别令人兴奋的治疗机会。这篇综述总结了当前的临床试验活动和整个生物药学领域启动的发现计划，并批判性地讨论了基于表观遗传的治疗在未来的PDAC治疗中的机会、障碍和限制。
Pancreatic ductal adenocarcinoma (PDAC) constitutes one of the most aggressive malignancies with a 5-year survival rate of <7%. Due to growing incidence, late diagnosis and insufficient treatment options, PDAC is predicted to soon become one of the leading causes of cancer-related death. Although intensified cytostatic combinations, particularly gemcitabine plus nab-paclitaxel and the folinic acid, fluorouracil, irinotecan, oxaliplatin (FOLFIRINOX) protocol, provide some improvement in efficacy and survival compared with gemcitabine alone, a breakthrough in the treatment of metastatic pancreatic cancer remains out of sight. Nevertheless, recent translational research activities propose that either modulation of the immune response or pharmacological targeting of epigenetic modifications alone, or in combination with chemotherapy, might open highly powerful therapeutic avenues in GI cancer entities, including pancreatic cancer. Deregulation of key epigenetic factors and chromatin-modifying proteins, particularly those responsible for the addition, removal or recognition of post-translational histone modifications, are frequently found in human pancreatic cancer and hence constitute particularly exciting treatment opportunities. This review summarises both current clinical trial activities and discovery programmes initiated throughout the biopharma landscape, and critically discusses the chances, hurdles and limitations of epigenetic-based therapy in future PDAC treatment.