The RPS6-NRF link was further confirmed by pharmacological inhibition of p-RPS6 in a xenograft model; treatment of the xenografted animals with the PI3K/mTOR inhibitor GSK458 alongside lapatinib reduced the growth of the HER2i-resistant tumor concurrently with downregulation of p-RPS6 and NRF2 proteins and the AKR1C1, AKR1C2, and AKR1B10 mRNAs in the xenograft tumor [354]. The gene discussed is PIK3CD; the disease is neoplasm.