Clinico-Pathologic and Biologic Predictors of EGFR Inhibitors Activity and Efficacy in Lung and in Colorectal Cancer

Maria   Anna   Bareschino; Clorinda      Schettino; Linda      Alvino; Cesare      Gridelli; Fortunato      Ciardiello

Abstract

The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor that is frequently overexpressed in several epithelial tumors. The EGFR was among the first cell membrane growth factor receptor to be proposed for cancer therapy and two EGFR targeted pharmacologic approaches have been successfully developed: monoclonal antibodies (MAbs) and small molecule inhibitors of the EGFR tyrosine kinase enzymatic activity (TKIs). These approaches have been tested in several human cancers, such as non small cell lung cancer (NSCLC), colorectal cancer (CRC), head and neck cancer and pancreatic cancer. However, only a subset of cancer patients will eventually benefit for the treatment with EGFR inhibitors. Therefore, the identification and the clinical validation of criteria for identifying patients which could more likely have a therapeutic advantage from the treatment with these drugs is a urgent clinical need. In the past few years, a series of reports have suggested that certain clinico-pathologic characteristics as well as specific gene alterations of the EGFR and of other genes such as K-RAS could help to identify patients whose cancers could be either sensitive or resistant to EGFR inhibitor therapy. Here we review the available clinical data which could help in defining a strategy to select patients for a more effective therapeutic use of anti-EGFR drugs.

Keywords: EGFR, erlotinib, gefitinib, cetuximab, panitumumab