By exclusively targeting activating mutations in the PI3K/AKT branch of mTOR signaling, it stands to reason that if these same cancers express mutation in LKB1 or express isoforms of the pseudokinase STRADα that render LKB1 catalytically deficient [7], the tumors may initially regress in response to treatment, however because AMPK activity is deregulated and the mTORC1-MAPK feedback loop is activated [8], the cancer will invariably return and/or be resistant to future treatments. The gene discussed is AKT1; the disease is cancer.