Recent Advances in Targeting the EGFR Signaling Pathway for the Treatment of Metastatic Colorectal Cancer

Abstract

Outcomes for metastatic colorectal cancer (mCRC) patients have been improved by treatment with anti-epidermal growth factor receptor (anti-EGFR) antibodies, particularly when combined with predictive biomarkers to select patients lacking RAS mutations. New technologies such as liquid biopsy and next-generation sequencing have revealed that potential mechanisms of resistance to anti-EGFR therapies act through acquired mutations of KRAS and the EGFR ectodomain. Mutations in cross-talking molecular effectors that participate in downstream EGFR signaling are also negative predictors for anti-EGFR therapy. In the current review, we describe recent advances in anti-EGFR therapy and discuss new treatment strategies to target downstream RAS-MAPK signaling in mCRC.

Keywords: chemotherapy; epidermal growth-factor receptor signaling (EGFR); metastatic colorectal cancer; secondary resistance.

Figure 1

Current strategies for targeting the epidermal growth factor receptor (EGFR) pathway. EGF receptors (Blue) activate survival signaling pathways including RAS/MAPK and PI3K/AKT signaling pathway leading to cell growth and proliferation. HGF/MET (green) signaling also promotes cell growth and proliferation through RAS/MAPK and STAT3 phosphorylation. Regular arrow: activates, Arrow ending with a straight line: inhibits.