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Critical Reviews™ in Oncogenesis
SJR: 0.946 SNIP: 0.503 CiteScore™: 2

ISSN Print: 0893-9675
ISSN Online: 2162-6448

Critical Reviews™ in Oncogenesis

DOI: 10.1615/CritRevOncog.v17.i1.60
pages 69-95

Targeting PI3 Kinase/AKT/mTOR Signaling in Cancer

Karen Sheppard
Division of Cancer Research, Peter MacCallum Cancer Centre , Department of Biochemistry and Molecular Biology
Kathryn M Kinross
Division of Cancer Research, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
Benjamin Solomon
Division of Cancer Research, Division of Cancer Medicine, and Sir Peter MacCallum Department of Oncology, and the Monash University, Clayton, Australia
Richard B. Pearson
Division of Cancer Research, Department of Biochemistry and Molecular Biology, Sir Peter MacCallum Department of Oncology, and the Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia
Wayne A. Phillips
Division of Cancer Research, Division of Cancer Surgery, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, and the Department of Surgery (SVH), University of Melbourne, Parkville, Australia

ABSTRACT

The phosphatidylinositol 3 kinase (PI3K) pathway is one of the major pathways modulating cell growth, proliferation, metabolism, survival, and angiogenesis. Hyperactivation of this pathway is one of the most frequent occurrences in human cancer and is thus an obvious target for treatment of this disease. Currently there are 26 novel compounds targeting the PI3K pathway being assessed in more than 150 cancer-related clinical trials. Although this pathway is involved in many vital biologic functions, data emanating from these clinical trials indicate that these drugs are well tolerated. This review outlines the interaction of the PI3K pathway with other signaling cascades, highlights mechanisms involved in hyperactivation, discusses current therapeutics in cancer-related clinical trials that target this pathway, and, based on preclinical data, discusses possible leads on patient selection and combinational therapy, including targeting multiple components of the associated signaling network.


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