Pancreatic cancer.
Pancreatic cancer.
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DOI：
10.1146/annurev.pathol.3.121806.154305
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
A. Maitra;R. Hruban
中科院分区：
文献类型：
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作者：
A. Maitra;R. Hruban
在过去的二十年里，我们对胰腺癌的了解有了爆炸式的发展，现在很清楚，胰腺癌是一种遗传（种系）和体细胞基因突变的疾病。胰腺癌中发生突变的基因包括KRAS2、p16/CDKN2A、TP53和SMAD4/DPC4，这些基因都伴随着大量的基因组和转录组改变，这些改变促进了细胞周期失调、细胞存活、侵袭和转移。胰腺癌不是从头开始的，已经确定了三种不同的前驱病变。胰腺癌的实验模型已经在基因工程小鼠中开发出来，它概括了这种同源人类疾病的多步骤进展。虽然胰腺癌的假定起源细胞仍然难以捉摸，但已经确定了具有干细胞样特性的少数细胞群，它们似乎与肿瘤的发生、转移和胰腺癌对常规治疗的抵抗有关。
The past two decades have witnessed an explosion in our understanding of pancreatic cancer, and it is now clear that pancreatic cancer is a disease of inherited (germ-line) and somatic gene mutations. The genes mutated in pancreatic cancer include KRAS2, p16/CDKN2A, TP53, and SMAD4/DPC4, and these are accompanied by a substantial compendium of genomic and transcriptomic alterations that facilitate cell cycle deregulation, cell survival, invasion, and metastases. Pancreatic cancers do not arise de novo, and three distinct precursor lesions have been identified. Experimental models of pancreatic cancer have been developed in genetically engineered mice, which recapitulate the multistep progression of the cognate human disease. Although the putative cell of origin for pancreatic cancer remains elusive, minor populations of cells with stem-like properties have been identified that appear responsible for tumor initiation, metastases, and resistance of pancreatic cancer to conventional therapies.