Dual targeting of HER3 and EGFR in colorectal tumors might overcome anti-EGFR resistance.

摘要: Multiple genetic alterations have been associated with resistance to anti-EGFR therapy in metastatic colorectal cancer (CRC) patients. Research has mainly focused on driver mutations KRAS, NRAS, BRAF and PI3K. However, recent evidence suggests a crucial role for non-genetic mechanisms conferring therapy. Specifically, the HER3 receptor is capable of heterodimerizing multiple EGFR family members resulting downstream activation PI3K MAPK pathways. Monoclonal antibodies targeted against are being investigated clinical trials; however, preliminary data shown limited activity. Thus, given relevance activating effector pathways therapy, therapeutic targeting combination primary drivers tumor also investigated. Here, we review as promoter discuss approaches that could potentially overcome this resistance.