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lüll The PIK3CA gene as a mutated target for cancer therapy Gustin JP; Cosgrove DP; Park BHCurr Cancer Drug Targets 2008[Dec]; 8 (8): 733-40The development of targeted therapies with true specificity for cancer relies upon exploiting differences between cancerous and normal cells. Genetic and genomic alterations including somatic mutations, translocations, and amplifications have served as recent examples of how such differences can be exploited as effective drug targets. Small molecule inhibitors and monoclonal antibodies directed against the protein products of these genetic anomalies have led to cancer therapies with high specificity and relatively low toxicity. Recently, our group and others have demonstrated that somatic mutations in the PIK3CA gene occur at high frequency in breast and other cancers. Moreover, the majority of mutations occur at three hotspots, making these ideal targets for therapeutic development. Here we review the literature on PIK3CA mutations in cancer, as well as existing data on PIK3CA inhibitors and inhibitors of downstream effectors for potential use as targeted cancer therapeutics.|*Mutation[MESH]|Class I Phosphatidylinositol 3-Kinases[MESH]|Enzyme Inhibitors/therapeutic use[MESH]|Humans[MESH]|Neoplasms/*drug therapy/genetics[MESH]|Phosphatidylinositol 3-Kinases/*genetics[MESH]|Phosphoinositide-3 Kinase Inhibitors[MESH]|Protein Kinases/drug effects[MESH]|Proto-Oncogene Proteins c-akt/antagonists & inhibitors[MESH]|TOR Serine-Threonine Kinases[MESH] |