## 4 Pancreatic Cancer  
Pancreatic cancer is known as one of the deadliest cancers worldwide. According to the American Cancer Society, in 2019, about 56,770 new cases of pancreatic cancer will be diagnosed and about 45,750 patients will die of this malignancy in the USA alone [www.cancer.org]. The overall five-year survival rate is about 6% [61]. The malignancy is highly fatal owing to a lack of effective screening methods and the fact that current treatment modalities fail to treat the disease [61; 62; 63]. The incidence of pancreatic cancer is similar in developing and developed countries and both sexes [www.cancer.org].  
The pancreas is composed of exocrine and endocrine cells. Exocrine cells form the exocrine glands and the ducts by which digestive enzymes and bicarbonate ions reach the small intestine, while the endocrine cells constitute the islets of Langerhans, which produce hormones such as insulin or glucagon [64]. Pancreatic cancers are distinguished according to the cells from which they originate, that is, exocrine cancers (adenocarcinomas) and pancreatic endocrine tumors (also named pancreatic neuroendocrine tumors, or NETs) [61].  
Exocrine pancreatic cancers originate from exocrine pancreatic cells and are the most common pancreatic cancers. Most exocrine pancreatic cancers are adenocarcinoma (pancreatic ductal adenocarcinoma, or PDAC) and account for about 85% of all pancreatic cancer cases [61]. PDAC has been described as a cancer associated with chronic inflammation, with pancreatitis being one of the main causes of its development. Patients with hereditary autoimmune pancreatitis have an estimated 40% risk of PDAC development, whereas those with chronic pancreatitis have a 13-fold greater risk [62].  
Risk factors for PDAC development are smoking, obesity, a diet rich in highly processed food and meat, diabetes (both type I and type II), allergies, male sex, and age--over 80% of pancreatic cancers develop between the ages of 60 and 80 years [65; 66]. It is estimated that 5%-10% of pancreatic cancers are hereditary and many inherited genetic disorders such as Lynch syndrome are reported to increase the risk of malignancy development [61]. Gene mutations related to PDAC include those in K-_ras_, occurring in more than 90% of human PDAC cases [67], as well as in _broa2_ and _cdkn2a_[65].  
Pancreatic endocrine tumours evolve from pancreatic endocrine tissue. NETs are very rare and account for 5% of all cases of pancreatic cancers [61]. NETs are classified according to the type of hormone they produce, that is, insulinoma (insulin), gastrinoma (gastrin), VIPoma (vasoactive intestinal peptide), and glucagonoma (glucagon) [68], and can serve as a basis for the development of other diseases. For example, insulinomas result in hypoglycemia, glucagonomas cause type I diabetes, and gastrinoma are associated with the Zollinger-Ellison syndrome. NETs are highly dependent on genetic factors, with a family history of sarcoma, gallbladder, ovarian or gastric cancers, or tuberous sclerosis, being predisposing factors to developing NETs. NET development is also associated with mutations in oncogenes such as _cend1_ and _men1_, tumour suppressor genes \(pRB\), \(p53\), and the cyclin-dependent kinase inhibitor (CKI) p16 INK4a, while a lesser role is played by environmental factors such as smoking or alcohol abuse [66].