Although we excluded patients with concurrent KRAS and PIK3CA mutations, activation of the PI3K pathway may as well be triggered by mutated KRAS directly, particularly in the presence of downstream MEK inhibition.20 In addition, reactivation of the MAPK pathway may occur as well, analogous to the observation with BRAF inhibition in BRAF-mutant CRC cells,21 especially when upstream receptors are not adequately inhibited. The gene discussed is PIK3CA; the disease is colorectal carcinoma.