RT Journal Article ID 6682d1d376eb582a A1 Sheppard, Karen A1 Kinross, Kathryn M A1 Solomon, Benjamin A1 Pearson, Richard B. A1 Phillips, Wayne A. T1 Targeting PI3 Kinase/AKT/mTOR Signaling in Cancer JF Critical Reviews™ in Oncogenesis JO CRO YR 2012 FD 2012-03-29 VO 17 IS 1 SP 69 OP 95 K1 phosphatidylinositol 3 kinase K1 anticancer drugs K1 targeted therapeutics K1 kinase inhibitors K1 combinational therapy K1 clinical trials AB 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. PB Begell House LK https://www.dl.begellhouse.com/journals/439f422d0783386a,07ff3a573b26d6e9,6682d1d376eb582a.html