Targeting the EGFR and the PKB pathway in cancer.

The EGFR and PKB pathways are frequently activated in cancer, so are prime targets for cancer therapy. To this end, new inhibitors are being tested. EGFR inhibitors as single therapy have little benefit, although therapies that evoke an antitumor immune response are more effective. Resistance mutations within the EGFR are common, as is activation of the antiapoptotic PKB pathway via alternative tyrosine kinase receptors, especially other EGFR family members or IGF1R. To combat resistance, multitargeted EGFR inhibitors and combined inhibition of the EGFR and PKB are being investigated. Inhibition of the EGFR and PKB pathways also sensitizes cancer cells to chemotherapy. Thus, EGFR and PI3K/PKB inhibitors will be most effective when used in rational combinations of targeted inhibitors and traditional chemotherapy.