Given that the PI3K pathway is frequently activated in cancers, that tumorigenesis and/or maintenance of the malignant phenotype of different tumor types is driven by its continued activation (Bader et al., 2005; Hollander et al., 2011), and that kinases are amendable to pharmacological intervention, it is not surprising that there has been great interest in the development of allosteric and ATP-competitive small molecule inhibitors targeting different components of this pathway downstream of RTKs (Liu et al., 2009). The gene discussed is PIK3CA; the disease is cancer.