Previous studies have revealed compensatory signaling mechanisms responsible for the drug resistance of HER2+ breast cancer, including: inactivation of PTEN tumor suppressor; antigen masking on HER2 epitope by MUC4; enhanced signaling through other ERBB family receptors; cross-talk of HER2 with IGF-1R; and mutational activation of downstream signaling through PI3-K/AKT pathway5, 6, 7, 8, 9. The gene discussed is PTEN; the disease is breast carcinoma.