Pancreatic cancer: evaluation of the activity of the immunomodulator P-MAPA against the inflammatory process chemically induced by 7,12-Dimethylbenz(a)antracene

Abstract

Although its lower global incidence, pancreatic cancer is considered an important disease due to its frequent late diagnoses, seeing that hardly presets early symptoms. Besides, the aggressiveness of this pathology associated with non-specificity of symptomatology leads the identification of pancreatic cancer just when the disease is in advanced stage. In general, this illness is normally diagnosed through axial computed tomography, although there are others diagnostic methods. From diagnoses, it is recommended staging followed by treatment strategy, that, in general, associate a resection surgery followed by chemotherapy adjuvant, being Gemcitabine the drug of first choice. However, due to the large number of side effects related with chemotherapy, a new drug, called P-MAPA is in development phase, to be used as an alternative to Gemcitabine in pancreatic cancer treatment. The immunotherapy with this drug allows the activation of innate immune system mediated by Toll-Like Receptors (TLR) 2 and 4, which are activated and initiate the translocation of Nuclear Factor kappa B (NFºB) and subsequent production of inflammatory molecules, such as Tumor Necrosis Factor alpha (TNF-±), Transforming growth factor beta (TGF-²) and some interleukins (IL), like IL-1 and IL-6. In short, with the activation of NFKB, the subsequent release of proinflammatory cytokines and chemokines will occur, these events being responsible for the activation of T cells. Thus, the present project aims at the study and characterization of the effects of immunotherapy with P-MAPA to be used as alternative to Gemcitabine in the treatment of pancreatic cancer, evaluating the Toll-like activation pathway (CD14, TLR2 and TLR4) and its subproducts in pro-inflammatory pathway (Myd88, NF-ºB, TNF-±, TGF-² and IL-6.