Department of Pathology, Beaujon Hospital - Paris Diderot University, Clichy, France.
Pathobiology. 2018;85(1-2):64-71. doi: 10.1159/000477773. Epub 2017 Aug 5.
Pancreatic adenocarcinoma is one of the deadliest malignancies worldwide, mainly due to frequent diagnosis at an advanced stage and its strong chemoresistance. Tumor heterogeneity is evident at the histological level, both between tumors and even within a tumor. Recent high-throughput analyses have confirmed that intertumor heterogeneity is greater than intratumor heterogeneity that is mostly driven by successive catastrophic genetic events in the early stage and by epigenetic modifications in the metastatic stage. While this heterogeneity may complicate the search for a universal cure, these analyses have distinguished several subtypes at the genomic, transcriptomic, and metabolomic levels that offer, for some, new therapeutic opportunities.
胰腺导管腺癌是全球最致命的恶性肿瘤之一,主要归因于其常在晚期诊断以及对化疗药物的强耐药性。肿瘤的异质性在组织学水平上是明显的,无论是在肿瘤之间还是甚至在一个肿瘤内。最近的高通量分析已经证实,肿瘤间异质性大于肿瘤内异质性,这主要是由早期阶段连续发生的灾难性遗传事件以及转移阶段的表观遗传修饰驱动的。虽然这种异质性可能使寻找普遍的治愈方法变得复杂,但这些分析已经在基因组、转录组和代谢组水平上区分出了几种亚型,为某些亚型提供了新的治疗机会。