Genetic and epigenetic biomarkers for diagnosis, prognosis and treatment of colorectal cancer

Figure 1 Representation of epidermal growth factor receptor pathway in response to therapy with anti-epidermal growth factor receptor inhibitors in wild-type and mutant patients. A: The binding of monoclonal antibodies (mAb) to EGFR normally causes the blockage (indicated with a red cross) of downstream RAS/RAF/MAPK and PI3K/AKT/mTOR signalling pathways and so the blockage of gene expression and cell cycle progression; B: Mutations in any gene of this pathway (indicated with a red star) cause a constitutive activation of the pathway leading to gene expression, upregulated proliferation, impaired differentiation and no response to monoclonal inhibitors. EGFR: Epidermal growth factor receptor; KRAS: v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog gene; BRAF: V-raf murine sarcoma viral oncogenes homolog B1; MEK: MAPK/ERK kinase; ERK: Extracellular signal-regulated kinases; PTEN: Phosphatase and tensin homolog; PI3K: Phosphatidylinositide-3-kinases; AKT: Protein Kinase B (PKB); mTOR: Mammalian target of rapamycin.