title: Targeting phosphoinositide 3-kinase pathways in pancreatic cancer--from molecular signalling to clinical trials.
abstract: Pancreatic cancer has one of the poorest prognoses among all cancers partly because of its silent nature and tendency for late discovery but also because of its persistent resistance to chemotherapy. At present there are very limited treatment alternatives for pancreatic cancer, hence the need to develop novel and more efficient drugs. It is well known that mutations in K-Ras oncogene accumulate early in the disease progression and occur in almost all of pancreatic ductal adenocarcinomas (PDAC). A key downstream target of the Ras family is phosphoinositide 3-kinase (PI3K), the enzyme responsible for generation of 3-phosphorylated phosphoinositides and activation of Akt (Protein Kinase B/Akt). The PI3K/Akt pathway is involved in inhibition of apoptosis and stimulation of cell proliferation and it is has been estimated that at least 50% of all cancer types are related to deregulation of this signalling pathway. In this review we will discuss how the PI3K/Akt/mTOR signaling network is altered in pancreatic cancer and further give an overview of preclinical and clinical studies where this pathway has been targeted.
authors.affiliation: Queen Mary University of London, Barts and The London School of Medicine and Dentistry, Blizard Institute of Cell and Molecular Science, Centre for Diabetes, Inositide Signalling Group, London, UK. m.falasca@qmul.ac.uk
authors.forename: Marco
authors.initials: M
authors.lastname: Falasca
authors.forename: Federico
authors.initials: F
authors.lastname: Selvaggi
authors.forename: Richard
authors.initials: R
authors.lastname: Buus
authors.forename: Sara
authors.initials: S
authors.lastname: Sulpizio
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Edling
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002986:Clinical Trials as Topic; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D019870:1-Phosphatidylinositol 4-Kinase