The 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. 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 p110α inhibitors and inhibitors of downstream
effectors for potential use as targeted cancer therapeutics.
Keywords: PIK3CA, mutation, oncogene, PI3 kinase, AKT, mTOR.
