Chronic Pancreatitis and Pancreatic Cancer

Abstract

Background: Pancreatic cancer (PC) is one of the most lethal diseases with an incidence rate almost equal to the rate of mortality. Chronic pancreatitis (CP) is a common chronic inflammatory disease of unknown etiology that affects the pancreas. Epidemiological studies have identified CP to be a major risk factor for PC. Summary: A greater understanding of the molecular mechanisms linking CP and PC has identified several common pathways that provide targets for future interventions. This article reviews those components in the CP-PC connection, including the role of macrophages, the maintenance of genome stability, cytokines, and other nodal factors such as nuclear factor kappa B, COX-2 and reactive oxygen species. Key Message: The molecular mechanisms that underlie CP and PC provide novel targets for future therapies for PC. Practical Implications: The stromal-desmoplastic reaction plays an important role in initiating and sustaining chronic inflammation and tumor progression. Recently, two targeted anti-tumor agents, erlotinib and nab-paclitaxel, have shown promising therapeutic efficacy. Notably, both these agents target components (EGFR and SPARC) within the inflammatory stroma surrounding malignant cells, underscoring the importance of inflammation in pancreatic carcinogenesis. Identifying the common pathways linking CP and PC may help uncover additional novel targets for future therapies.

Risk of pancreatic cancer in patients undergoing surgery for chronic pancreatitis

“…Based on reports, pancreatic acinar contains a sufficient activity level of Ras, which proves that CP is directly linked with pancreatic cancer [14]. In addition, both pancreatic cancer tissue and CP have same dysregulated signaling pathways, such as nuclear factor kappa B, cytokines, peroxisome proliferator-activated receptor-γ, as well as reactive oxygen species [15]. However, there is possibly no identical genetic susceptibility between pancreatic cancer and CP, at least in the variants with high frequency [16].…”

Adipocyte and lipid metabolism in cancer drug resistance

“…Nonmalignant cells, including adipocytes, constitute a substantial proportion of the tumor mass, and their contents are often correlated with a fast-growing and invasive phenotype. For example, the fibrotic component in some PDAC can occupy more than 90% of the entire tumor mass, and the degree of fibrosis is inversely correlated with the survival prognosis (111). As noncancer cells are common in the TME of all solid tumors, drugs targeting these cells are often used to treat various cancers and produce beneficial effects in human patients.…”

The EGFR-HSF1 axis accelerates the tumorigenesis of pancreatic cancer

“…In addition, studies have proven that both acute and chronic pancreatitis are the key risk factors for pancreatic cancer [26][27][28], so we treated 8-week-old KC mice (when PanINs lesions starting formation, as shown in Additional le 1: Fig. S1E) with cerulein to induce pancreatitis, and we found that HSF1 was expressed at a high level and had translocated from the cytoplasm to the nucleus during the pancreatitis ( Fig.…”