Signalling pathways passing Src in pancreatic endocrine tumours: relevance for possible combined targeted therapies.

摘要: The most frequent molecular abnormalities in pancreatic endocrine tumours (PETs) are mutations of the MEN1 gene, deregulation PI3K/AKT/mTOR signalling pathway and overactivation growth factors their receptors, such as VEGF. On this basis, everolimus (Afinitor®; Novartis) sunitinib (Sutent®; Pfizer) have both been approved by FDA for treatment progressive, unresectable, locally advanced or metastatic PETs. However, surrogate markers able to predict response PET patients with these drugs not available, cancer cells treated targeted therapies might develop escape pathways that evoke pro-survival feedback responses. existence cross-talk between different PETs has poorly investigated. In present review, we data supporting an important role Src family kinases (SFKs) PETs, together recent observation a novel SFK modulating mTOR activity. Of note, while triggered activation survival dependent on PI3K/AKT vitro, simultaneous inhibition SFKs blocked unwanted signal. These studies set ground investigation combined inhibitors.