A comprehensive review of pancreatic cancer and its therapeutic challenges

Abstract

Pancreatic cancer is a devastating and lethal human malignancy with no curable chemo-treatments available thus far. More than 90% of pancreatic tumors are formed from ductal epithelium as pancreatic ductal adenocarcinoma (PDAC), which often accompany with the expression of mutant K-ras. The incidences of pancreatic cancer are expected to increase rapidly worldwide in the near future, due to environmental pollution, obesity epidemics and etc. The dismal prognosis of this malignancy is contributed to its susceptibility to tumor micro-metastasis from inception and the lack of methods to detect precursor lesions at very early stages of the onset until clinical symptoms occur. In recent years, basic and clinical studies have been making promising progresses for discovering markers to determine the subtypes or stages of this malignancy, which allow effectively implementing personalized therapeutic interventions. The purpose of this review is to discuss the existing knowledge of the molecular mechanisms of pancreatic cancer and the current state of treatment options with the emphasis on targeting therapeutic approaches. The specific focuses are on the molecular mechanisms of the disease, identifications of drug resistance, establishment of immune escaping mechanisms as well as potential of targeting identified pathways in combinations with existing chemo-drugs.www.aging-us.com AGINGpancreatic cancer risk and onset. The majority of the incidences of pancreatic cancer occur sporadically and the disease is often accompanied with genetic abnormalities in somatic cells. Studies have indicated that unlike familial cancer syndromes for gastrointestine/colon or breast, pancreatic cancer has very low penetrance with less than 10% of the cases to be linked to a familial setting [3,4]. Among many genetic lesions detected in pancreatic cancer, active mutant K-ras is one that occurs in early stages of pancreatic tumorigenesis, followed by inactivation of several tumor suppressors, including p53, p16 INK4a , and others (such as SMAD4/DPC4, MLH1, LKB1, PRSS1, and BRCA2) [3,4].

Is Helicobacter pylori infection associated with pancreatic cancer? A systematic review and meta-analysis of observational studies

“…This widespread seropositivity could potentially distort the association findings. Fifth, almost all included studies did not identify the specific type of pancreatic cancer with the exception of the study conducted by Raderer et al 35 The fact, however, is that more than 90% of pancreatic cancer is pancreatic ductal adenocarcinoma; 60 we therefore believe that the pathological type has little impact on the outcome. Finally, only three cohort studies evaluated the relationship between H. pylori infection and risk of incident pancreatic cancer.…”

The Potent G-Quadruplex-Binding Compound QN-302 Downregulates S100P Gene Expression in Cells and in an In Vivo Model of Pancreatic Cancer

“…Pancreatic cancer, of which the most common form by far is pancreatic ductal adenocarcinoma (PDAC), is one of the most intractable of all human cancers [ 1 , 2 , 3 ]. Early stages of the disease are largely asymptomatic, so presentation is commonly at stages 2–4.…”

Pancreatic cancer and fibrosis: Targeting metabolic reprogramming and crosstalk of cancer-associated fibroblasts in the tumor microenvironment

“…Diabetes associated with obesity and chronic pancreatitis also show a relevance to pancreatic cancer (5). Surgery is the treatment that has the potential to cure pancreatic cancer now, whilst chemotherapy, immunotherapy and targeted therapies have been demonstrated to help enhance the overall survival rate of patients (6)(7)(8).…”