![]() Studies from several laboratories in the 1980s established that activated growth factor receptors and oncoproteins associate with an enzyme that phosphorylates PtdIns ( Sugimoto et al., 1984 Whitman et al., 1985). The head group of phosphatidylinositol can be phosphorylated on three of the free hydroxyls to form seven different phosphoinositide species with distinct roles in vesicle trafficking and signal transduction. Reversible phosphorylation of inositol lipids controls diverse functions in cells. We also discuss recent progress developing PI3K-targeted therapies for treatment of cancer and other diseases. ![]() Here we provide a perspective on the roles of class I PI3Ks in the regulation of cellular metabolism and in immune system functions, two topics closely intertwined with cancer biology. Many of these functions impinge upon oncology by influencing the efficacy and toxicity of PI3K-targeted therapies. In parallel to PI3K research by cancer biologists, investigations in other fields have uncovered exciting and often unpredicted roles for PI3K catalytic and regulatory subunits in normal cell function and in disease. Many PI3K pathway-targeted therapies have been tested in oncology trials, resulting in regulatory approval of one isoform-selective inhibitor (idelalisib) for treatment of certain blood cancers, and a variety of other agents at different stages of development. Phosphoinositide 3-kinase (PI3K) activity is stimulated by diverse oncogenes and growth factor receptors, and elevated PI3K signaling is considered a hallmark of cancer.
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