Simultaneous targeting of EGFR and mTOR inhibits the growth of colorectal carcinoma cells.

Epidermal growth factor receptor (EGFR) is highly expressed in colorectal carcinomas and, as a result, it leads to the activation of downstream mammalian target of rapamycin (mTOR) kinase pathways for cancer growth and progression. Clinical and preclinical studies, however, have shown that inhibition of epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR) alone is not sufficient to treat colorectal carcinomas. In search of effective combination therapies, we show here that simultaneous targeting of EGFR with its inhibitor, erlotinib and mTOR with its inhibitor, rapamycin inhibits the phosphorylation and activation of downstream phosphatidylinositol 3-kinase (PI3K), Akt, mTOR and extracellular-signal-regulated kinase 1/2 (Erk1/2) pathways, resulting in the inhibition of cell cycle progression and the growth of both KRAS wild-type and mutated colorectal carcinoma cells. This study has demonstrated the principle that the combination of erlotinib and rapamycin may provide an effective therapy for colorectal carcinomas.