Cancer of the Pancreas: Molecular Pathways and Current Advancement in Treatment

Abstract

Pancreatic cancer is one of the most lethal cancers among all malignances, with a median overall survival of <1 year and a 5-year survival of ~5%. The dismal survival rate and prognosis are likely due to lack of early diagnosis, fulminant disease course, high metastasis rate, and disappointing treatment outcome. Pancreatic cancers harbor a variety of genetic alternations that render it difficult to treat even with targeted therapy. Recent studies revealed that pancreatic cancers are highly enriched with a cancer stem cell (CSC) population, which is resistant to chemotherapeutic drugs, and therefore escapes chemotherapy and promotes tumor recurrence. Cancer cell epithelial to mesenchymal transition (EMT) is highly associated with metastasis, generation of CSCs, and treatment resistance in pancreatic cancer. Reviewed here are the molecular biology of pancreatic cancer, the major signaling pathways regulating pancreatic cancer EMT and CSCs, and the advancement in current clinical and experimental treatments for pancreatic cancer.

Liquid biopsy in pancreatic ductal adenocarcinoma: current status of circulating tumor cells and circulating tumor DNA

“…Marker combinations of CD44, CD24, and epithelial-specific antigen (ESA) were also identified as indicators of pancreatic CSCs . Other putative markers for pancreatic CSCs include c-Met, doublecortin-like kinase 1, and CD44v6 (Polireddy and Chen, 2016). A recent study by Poruk et al evaluated 60 consecutive PDAC patients undergoing surgery.…”

ROCK signalling induced gene expression changes in mouse pancreatic ductal adenocarcinoma cells

“…The most common form is pancreatic ductal adenocarcinoma (PDAC), with the majority of patients carrying activating KRAS oncogene mutations and mutation or deletion of the TP53 tumour suppressor 9 . Furthermore, exome sequencing of pancreatic cancer genomes revealed that ~15% of pancreatic cancer patients carry ROCK1 gene amplifications 10 .…”

Vasohibin 2 promotes malignant behaviors of pancreatic cancer cells by inducing epithelial‐mesenchymal transition via Hedgehog signaling pathway

“…Epithelial-mesenchymal transition (EMT), a transient and reversible process in which polarized epithelial cells acquire a fibroblastoid or mesenchymal phenotype, is associated with the high motility, invasiveness, metastasis, and drug resistance of tumor cells. [4][5][6] Cells that have undergone EMT exhibit cancer stem cell-like features and are able to invade across basement membranes and stromal tissues. 7 Our previous study has shown that EMT correlates with cancer stem cell-like phenotypes, mainly increased proportion of CD24 + CD44 + and CD133 + cells in PC.…”