On the basis of these experimental results it has been hypothesized that a double blockade of the HER2/PIK3CA/AKT/mTOR pathway with the combination of neratinib, a pan c-erb inhibitor (to prevent compensatory upregulation of phosphorylated (p)HER2/neu and pEGFR) and taselisib, a PIK3CA inhibitor (to prevent downstream upregulation of pAKT in neratinib-treated/resistant tumors) may represent a more effective approach to prevent or significantly delay the development of tumor resistance in endometrial cancer patients. The gene discussed is PIK3CA; the disease is endometrial cancer.