Platinum treated ovarian cancer patients with complete responses and patients with more than 6 months of progression free survival were reported to be less likely to have PIK3CA genomic alterations at presentation than people who relapsed within 6 months. Conversely, over-expression of XIAP, a direct inhibitor of caspase 3/7, promotes AKT phosphorylation and reduces cisplatin induced apoptosis. Pei et al. showed that FKBP51, which encourages the dephosphorylation of AKT S473, is associated Lapatinib Tykerb with sensitivity to chemotherapy, but not specifically platinum agents. PTEN expression has been observed to correlate with chemosensitivity in ovarian cancer cell lines and PTEN modulation can alter sensitivity to cisplatin. Nevertheless, the studies discussed here found in vitro generated models of resistance Immune system that don’t occur by the same processes as the in vivo derived lines described here, and these studies did not address the direct link between platinum induced DNA damage and AKT activation that suggest a nuclear AKT phosphorylation function that’s different from the canonical activation pathway at the cell surface. Data presented here indicate that prolonged activation of AKT in response to cisplatin exposure is a feature acquired on the development of clinical resistance to cisplatin inside an individual patient. Enhancement of apoptosis and accumulation of nuclear AKT are only observed in clinically resistant cells and not in their sensitive and painful matched competitors, further suggesting that AKT service prevents cisplatininduced apoptosis as a mechanism of clinically acquired resistance. Numerous AKT inhibitors are in development with several in phase 1/2 tests, and therefore combining AKT inhibition with main-stream platinum therapy is a possible Ibrutinib Src inhibitor technique for handling clinically acquired platinum resistance. Curiously, but, inhibition of AKT, or certainly IGF 1R or mTOR, is associated with diabetes and hyperglycemia. AKT is an essential component of the insulin signaling pathway being activated in response to insulin stimulation through phosphorylation by PDK1/mTORC2. Triggered AKT causes translocation of GLUT4 to the plasma membrane facilitating glucose uptake while also inactivating GSK 3, thus improving glycogen synthesis. Moreover, AKT phosphorylates and inhibits the transcription factor FOXO1, which may suppress glucose production in the liver and kidney by down-regulation of phosphoenolpyruvate carboxykinase and glucose 6 phosphatase. Additionally, active AKT phosphorylates the TSC1 TSC2 complex, leading to mTOR initial, which regulates protein synthesis/cell development in response to insulin.