Abstract
Receptor tyrosine kinase pathways are frequently deregulated in cancer. Inhibiting these pathways with small molecule inhibitors or monoclonal antibodies has become a crucial addition to the therapeutic armamentarium in oncology. Since the introduction of drugs that target receptor tyrosine kinase pathways, it has become evident that not all patients respond to treatment. Therefore, biomarkers to predict response and benefit of drugs targeting tyrosine kinases have been sought. Monoclonal antibodies targeting the Epidermal Growth Factor Receptor (EGFR), one of the four receptors of the EGFR family were among the first targeted therapies used in solid tumors. Two drugs of this class, cetuximab and panitumumab, have been used in patients with metastatic colorectal cancer initially without any biomarker requirement. Soon, it became clear that responses were mostly observed in patients without mutations in KRAS oncogene. Currently, additional mutations of the pathway, including non-exon 2 mutations in KRAS, mutations in the homologous GTPase NRAS, in kinase BRAF and PIK3CA and other pathway proteins, have been added in the evaluation for responsiveness prediction to cetuximab and panitumumab. In this review, the predictive biomarker landscape for anti-EGFR monoclonal antibody inhibitors in metastatic colorectal cancers with no extended RAS and BRAF mutations will be examined.