胰腺导管腺癌(PDAC)是最致命的肿瘤类型之一。其发病率在全球范围内呈上升趋势。尽管在早期发现这些肿瘤时,手术切除可以提高生存率,这种癌症通常是无症状的,并且疾病只有在转移后才变得明显。几个危险因素与这种疾病相关,最相关的是慢性胰腺炎,糖尿病,烟草和酒精的摄入量,镉,砷和铅暴露,某些传染病,以及与家族成分相关的一些基因的突变状态。PDAC发病率近几十年来有所增加,化疗治疗的替代方案很少。内质网(ER)应激因子,如GRP78/BiP(78kDa葡萄糖调节蛋白),ATF6α(激活转录因子6同工型α),IRE1α(需要肌醇的酶1同工型α),和PERK(蛋白激酶RNA样内质网激酶)激活与存活和凋亡有关的几种基因的转录。这些因素中的一些有助于在癌症中诱导称为休眠的非增殖状态。调节内质网应激可诱导肿瘤细胞休眠,从而延长患者的生存期。在这次系统审查中,我们已经收集了与PDAC有关的内质网应激因子的相关结果,我们分析了与内质网应激相关的休眠机制及其作为抗PDAC化疗靶点的潜在用途。
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of tumours, and its incidence is rising worldwide. Although survival can be improved by surgical resection when these tumours are detected at an early stage, this cancer is usually asymptomatic, and disease only becomes apparent after metastasis. Several risk factors are associated with this disease, the most relevant being chronic pancreatitis, diabetes, tobacco and alcohol intake, cadmium, arsenic and lead exposure, certain infectious diseases, and the mutational status of some genes associated to a familial component. PDAC incidence has increased in recent decades, and there are few alternatives for chemotherapeutic treatment. Endoplasmic reticulum (ER) stress factors such as
GRP78/BiP (78 kDa glucose-regulated protein), ATF6α (activating transcription factor 6 isoform α), IRE1α (inositol-requiring enzyme 1 isoform α), and PERK (protein kinase RNA-like endoplasmic reticulum kinase) activate the transcription of several genes involved in both survival and apoptosis. Some of these factors aid in inducing a non-proliferative state in cancer called dormancy. Modulation of endoplasmic reticulum stress could induce dormancy of tumour cells, thus prolonging patient survival. In this systematic
review, we have compiled relevant results concerning those endoplasmic reticulum stress factors involved in PDAC, and we have analysed the mechanism of dormancy associated to endoplasmic reticulum stress and its potential use as a chemotherapeutic target against PDAC.