Skip to main content
Fig. 1 | Journal of Experimental & Clinical Cancer Research

Fig. 1

From: Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies

Fig. 1

Intrinsic mechanisms of resistance to anti-EGFR mAbs in metastatic colorectal cancer. The intrinsic mechanisms include abnormal activation of oncogenic signalling pathways, aberrant gene expression, metabolic disorders, increased autophagy function and cancer stem cells. For example, genomic alterations and proteic phosphorylation induce activation of the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR cascades. ERBB2/MET amplification and abnormal IGF-1R activation stimulate compensatory feedback loop signalling of EGFR. The phenotype shift of cancer stem cells (CSCs) into epithelial-to-mesenchymal transition (EMT) contributes to therapy resistance. Glycolysis, lipid synthesis, fatty acid oxidation and vitamin deficiency in cancer cells also reduced the efficiency of EGFR-targeted therapy. The agents for specific points are also shown in the figure. Abbreviations: CSC, cancer stem cell; EMT, epithelial-to-mesenchymal transition; PI3K, phosphoinositide 3-kinase; IGF-1R, insulin-like growth Factor 1 receptor

Back to article page