Resistance to rapamycin has been previously reported for breast cancer and renal cell carcinoma36,46, and various mechanisms have been postulated, including a shift in the balance from the rapamycin-sensitive mTORC1 to the rapamycin-insensitive mTORC2, increased expression of phospholipase D47, re-activation of AKT and MAPK signaling pathways, and acquisition of mutations in the FRB and kinase domains of mTOR in a variety of tumors36. The gene discussed is FOLR2; the disease is breast cancer.