Targeting a Novel Phosphoinositide Signaling Pathway for Cancer Therapy

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Dramatic advances in cancer treatment will depend on identifying new targets for therapeutics. Here we propose as a candidate target a novel phosphoinositide signaling pathway that we have discovered. We have identified a pathway involving the phosphoinositide PtdIns(4)P and a new protein that binds to it which we have called PI4P-BP. We have shown that this pathway is required for normal Golgi architecture and function. Cancer cells often require autocrine, paracrine, or endocrine growth factor signaling for continued proliferation and survival. Since trafficking of growth factors and growth factor receptors requires intact Golgi function, interference with the Golgi is expected to interfere with cancer proliferation and survival. We have devised methods to inducibly interfere with the PtdIns(4)P/PI4P-BP pathway. We propose experiments to determine the effect of interference with the PtdIns(4)P/PI4P-BP pathway on growth factor signaling and thus whether it will be worthwhile to develop this novel therapeutic strategy further toward its clinical application.