Targeting Phosphoinositide 3-Kinase Pathways in Pancreatic Cancer – from Molecular Signalling to Clinical Trials

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Editor-in-Chief:
Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


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Targeting Phosphoinositide 3-Kinase Pathways in Pancreatic Cancer – from Molecular Signalling to Clinical Trials



Anti-Cancer Agents in Medicinal Chemistry, 11(5): 455-463.

Author(s): Marco Falasca, Federico Selvaggi, Richard Buus, Sara Sulpizio and Charlotte E Edling.

Affiliation: Queen Mary University of London, Barts and The London School of Medicine and Dentistry, BlizardInstitute of Cell and Molecular Science, Centre for Diabetes, Inositide Signalling Group, London E1 2AT, UK.

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 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 signalling network is altered in pancreatic cancer and further give an overview of preclinical and clinical studies where this pathway has been targeted.

Keywords:

Akt, drug treatment, K-Ras, Mtor, pancreatic cancer, pancreatic ductal adenocarcinoma, phosphatidylinositol 3-kinase.



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Article Details

Volume: 11
Issue Number: 5
First Page: 455
Last Page: 463
Page Count: 9
DOI: 10.2174/187152011795677382
Price: $58
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