Therapeutic strategies should therefore be designed with the recognition that oncogenic signalling through PIK3CA-mutation and PTEN-loss are distinct, and should be based on comprehensive mutational analysis, tumor subtyping, identification of cooperating oncogenic events and ultimately direct assessment of tumor response to anti-PI3K/AKT/mTOR and anti-RAS/MAPK therapies. The gene discussed is MTOR; the disease is neoplasm.