MK-2206 + gefitinib

MK-2206 + gefitinib is a combination therapy that pairs MK-2206, a potent allosteric Akt inhibitor, with gefitinib, a small molecule inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase. This combination has demonstrated synergistic cytotoxic effects against cancer cells, particularly in glioma and EGFR-mutant non-small cell lung cancer. The combination works by simultaneously inhibiting two critical cancer signaling pathways: EGFR signaling (via gefitinib) and the PI3K/Akt pathway (via MK-2206). This dual inhibition enhances both apoptotic and autophagic effects in cancer cells, with studies showing that the combination can switch from promoting autophagy to promoting apoptosis over time.