Exploring the therapeutic potential of focal adhesion kinase inhibition in overcoming chemoresistance in pancreatic ductal adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is among the leading causes of cancer-related deaths worldwide. Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase often overexpressed in PDAC. FAK has been linked to cell migration, survival, proliferation, angiogenesis and adhesion. This review first highlights the chemoresistant nature of PDAC. Second, the role of FAK in PDAC cancer progression and resistance is carefully described. Additionally, it discusses recent developments of FAK inhibitors as valuable drugs in the treatment of PDAC, with a focus on diamine-substituted-2,4-pyrimidine-based compounds, which represent the most potent class of FAK inhibitors in clinical trials for the treatment of PDAC disease. To conclude, relevant computational studies performed on FAK inhibitors are reported to highlight the key structural features required for interaction with the protein, with the aim of optimizing this novel targeted therapy.