Pancreatic Carcinogenesis

Abstract

Pancreatic cancer is an almost universally lethal disease. Research over the last two decades has shown that pancreatic cancer is fundamentally a genetic disease, caused by inherited germline and acquired somatic mutations in cancer-associated genes. Multiple alterations in genes that are important in pancreatic cancer progression have been identified, including tumor suppressor genes, oncogenes, and genome maintenance genes. Furthermore, the identification of noninvasive precursor lesions of pancreatic adenocarcinoma has led to the formulation of a multi-step progression model of pancreatic cancer and the subsequent identification of early and late genetic alterations culminating in invasive cancer. In addition, an increased understanding of the molecular basis of the disease has facilitated the identification of new drug targets enabling rational drug design. The elucidation of genetic alterations in combination with the development of high-throughput sensitive techniques should lead to the discovery of effective biomarkers for early detection of this malignancy. This review focuses mainly on the current knowledge about the molecular insights of the pathogenesis of pancreatic ductal adenocarcinoma.

Hedgehog signaling pathway regulates human pancreatic cancer cell proliferation and metastasis

“…Chemotherapies and radiotherapies are largely ineffective, and metastatic disease frequently recurs even after surgical resection of primary lesions (2)(3)(4). Recently, a number of risk factors have been identified, including age, cigarette smoking, high dietary intake of meat and fat, low serum folate levels, obesity, long-standing diabetes mellitus, chronic pancreatitis and family history (5), but exactly how these risk factors contribute to carcinogenesis remains largely unknown. Therefore, novel strategies for the prevention of tumor progression and metastasis are urgently needed.…”

Induction of CTLs by DCs pulsed with K-ras mutant peptide on the surface of nanoparticles in the treatment of pancreatic cancer

“…The K-ras gene point mutation generally occurs in codons 12, 13 and 61, with a highest mutation rate at codon 12. Research has shown that the K-ras gene mutation rate in pancreatic cancer is approximately 90% (19). It has been found that a point mutation of codon 12 of the K-ras gene is an early event in pancreatic cancer (20).…”

Werner syndrome as a hereditary risk factor for exocrine pancreatic cancer

“…Of particular note in the 43-year-old patient's tumor was the absence of the oncogenic K-RAS mutations, especially as mutations that constitutively activate K-RAS signaling have been identified in more than 95% of sporadic pancreatic adenocarcinoma. 4 Taken together, the clinicopathologic findings and molecular features of pancreatic adenocarcinoma in these patients with WS raise the possibility of a causal relationship between development of pancreatic adenocarcinoma and their underlying WS.…”

“…4 Pancreatic intra-epithelial neoplasia (PanIN) initially exhibit genomic instability and senescence-associated telomere shortening. 5,6 Progression of PanIN to invasive adenocarcinoma is accompanied by aberrant activation of Hedgehog signaling, oncogenic K-RAS mutations signs of WS, including premature graying of hair, diffuse muscular and dermal atrophy, voice changes and classic "bird-like facies" (Fig.…”