AUTHOR=Ferreira Roseane Guimarães , Narvaez Luis Eduardo Mosquera , Espíndola Kaio Murilo Monteiro , Rosario Amanda Caroline R. S. , Lima Wenddy Graziela N. , Monteiro Marta Chagas TITLE=Can Nimesulide Nanoparticles Be a Therapeutic Strategy for the Inhibition of the KRAS/PTEN Signaling Pathway in Pancreatic Cancer? JOURNAL=Frontiers in Oncology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.594917 DOI=10.3389/fonc.2021.594917 ISSN=2234-943X ABSTRACT=

Pancreatic cancer is an aggressive, devastating disease due to its invasiveness, rapid progression, and resistance to surgical, pharmacological, chemotherapy, and radiotherapy treatments. The disease develops from PanINs lesions that progress through different stages. KRAS mutations are frequently observed in these lesions, accompanied by inactivation of PTEN, hyperactivation of the PI3K/AKT pathway, and chronic inflammation with overexpression of COX-2. Nimesulide is a selective COX-2 inhibitor that has shown anticancer effects in neoplastic pancreatic cells. This drug works by increasing the levels of PTEN expression and inhibiting proliferation and apoptosis. However, there is a need to improve nimesulide through its encapsulation by solid lipid nanoparticles to overcome problems related to the hepatotoxicity and bioavailability of the drug.