Clinical Implications and Quality Assurance of Molecular Testing for EGFR-Targeting Agents in Colorectal Cancer
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The introduction in clinical practice of anti-epidermal growth factor receptor (EGFR) antibodies has improved the clinical outcome of metastatic colorectal cancer (mCRC) patients. Nevertheless, only 10% of mCRC tumors respond to these treatments, thus rendering the efforts made to maximize their therapeutic index justified. Although several biomarkers have been identified, we do not know yet how to administer these drugs in colorectal cancer patients in a “personalized–targeted manner.” With this review we will try to demonstrate that we need to go beyond the assumption of a binary relationship between one genetic event and response or resistance to anti-EGFR drugs and that several factors can influence the response to these agents. Therefore, the introduction in future approaches of a holistic genomic discovery plan instead of an individual and specific identification of alterations is needed.
KeywordsMetastatic colorectal cancer EGFR dependency Anti-EGFR treatments Cetuximab Panitumumab Anti-EGFR moAbs Personalized cancer medicine Colorectal cancer subgroups Molecular subgroups KRAS BRAF PI3KCA NRAS PTEN Amphiregulin Epiregulin HER2 amplification Gene module Gene expression profile FcγRIIa FcγRIIΙa Let7 Anti-EGFR sensitivity Anti-EGFR resistance KRAS testing
Loredana Vecchione and Zenia Saridaki equally contributed in manuscript writing. Zenia Saridaki is a recipient of a research fellowship from the Hellenic Society of Medical Oncology.
L. Vecchione: none; Z. Saridaki: none; S. Tejpar: honoraria from and educational presentations/speakers’ bureau for Merck Serono.
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