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Somatic mutations in PI3Kalpha: structural basis for enzyme activation and drug design Gabelli SB; Mandelker D; Schmidt-Kittler O; Vogelstein B; Amzel LMBiochim Biophys Acta 2010[Mar]; 1804 (3): 533-40The PI3K pathway is a communication hub coordinating critical cell functions including cell survival, cell growth, proliferation, motility and metabolism. Because PI3Kalpha harbors recurrent somatic mutations resulting in gains of function in human cancers, it has emerged as an important drug target for many types of solid tumors. Various PI3K isoforms are also being evaluated as potential therapeutic targets for inflammation, heart disease, and hematological malignancies. Structural biology is providing insights into the flexibility of the PI3Ks, and providing basis for understanding the effects of mutations, drug resistance and specificity.|*Phosphoinositide-3 Kinase Inhibitors[MESH]|Animals[MESH]|Antineoplastic Agents/*chemistry/pharmacokinetics/therapeutic use[MESH]|Cell Movement/drug effects[MESH]|Cell Proliferation/drug effects[MESH]|Cell Survival/drug effects[MESH]|Enzyme Activation/drug effects/genetics[MESH]|Enzyme Inhibitors/*chemistry/pharmacology/therapeutic use[MESH]|Humans[MESH]|Isoenzymes/antagonists & inhibitors/genetics/metabolism[MESH]|Neoplasms/*drug therapy/enzymology/genetics[MESH]|Phosphatidylinositol 3-Kinases/*genetics/metabolism[MESH]|Protein Structure, Tertiary/genetics[MESH]|Signal Transduction/drug effects[MESH] |
