Rapamycin analogs (“rapalogs”; glossary box) were the first PI3K pathway inhibitors to be tested in clinical trials for the treatment of cancer, and Everolimus and Temsirolimus have been approved by the US Food and Drug Administration (FDA) for the treatment of advanced renal cell carcinoma (ARCC), and Everolimus has also been approved for the treatment of progressive neuroendocrine tumors of pancreatic origin and non-malignant kidney and brain tumors (Table 1). The gene discussed is PIK3CA; the disease is cancer.