However, upregulated PI3K-Akt-mTOR signaling is clearly associated with chemoresistance, which has been shown in various preclinical cancer models, and chemotherapy response can be augmented in this setting by simultaneous PI3K or Akt inhibition [10, 11, 22–24], in particular in ER positive breast cancer [10, 22]. The gene discussed is PIK3CA; the disease is breast cancer.