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Infiltrating ductal adenocarcinoma of the pancreas, referred to as “pancreatic cancer” is an aggressive metastatic cancer with a high mortality rate. The 5 year survival rate is less than 5 %.

Pancreatic cancer arises as a consequence of inherited and acquired mutations in cancer associated genes. The most common antecedent lesions of pancreatic cancer are called pancreatic intraepithelial neoplasias (PanINs).

Sequencing the pancreatic cancer genome has confirmed 4 genes that are most commonly affected by somatic mutations: KRAS, CDKNA2A/p16, SMAD4, and TP53.

In recent studies is reported that cancer cells depend on IL-17B receptor (IL-17BR) signaling cascade for their metastatic and malignant properties. The interactions between malignant cells and the microenvironment are very tight and robust. The microenvironment includes abundant extracellular matrix, fibroblasts, proinflammatory macrophages, which contribute to form a dense barrier to chemotherapeutic and immune assault against these cancer cells.

Latest studies suggests that IL-17B and IL-17BR support the anchorage-independent growth, tumorigenecity and metastasis of pancreatic cancer cells. Scientists demonstrated that treatment with a monoclonal antibody targeting IL-17RB extended survival in an orthotropic xenograft model.

Apart this study, another study suggests that IL-17 signaling is needed during all stages of cancerogenesis from non-invasive forms to metastatic spread.

Other clinical trials of IL-17 inhibition are being observed in a variety of proinflammatory conditions such as: psoriasis, rheumatoid arthritis.

Apart all the result of the studies made until now, it is possible that protumorigenic IL-17 activity is confined to a specific subset of patients with pancreatic cancer. A study suggests that ~ 40% of pancreatic cancers display detectable IL-17BR in IHC (immunohistochemistry).

Despite the fact that these studies have different point of views it is believed that interrupting interleukin cascade signalization will soon become an important therapeutic option.

 

 

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Image adopted from: http://jem.rupress.org/content/212/3/284/F2.large.jpg

http://jem.rupress.org/content/212/3/284

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