Mechanism of EGER-related cancer drug resistance.

Drug resistance in cancer arises from a complex range of biochemical and molecular events, which ultimately result in tumor cell survival. Identifying key genes and signal pathways involved in the molecular mechanisms of drug resistance is essential for establishment of new drug targets for preventing further resistance development and spreading. Epidermal growth factor receptor (EGFR) was the first growth factor receptor proposed as a target for cancer therapy. Significant progress in studying EGFR gene expression and mutation has been made in understanding the molecular events involved in EGFR-targeted agents. Recently, some individual chromosomal features such as EGFR copy number variation were demonstrated as new aspects related to drug sensitivity. Identifying these functional regulators of drug resistance will benefit therapeutic decision-making. In this study, we describe an extensive investigation of the published literature on mutation, amplification, and expression of EGFR and its downstream signaling that directly contribute to EGFR inhibitor resistance, including the gene status of KRAS, BRAF, PIK3CA, PTEN, MEK, and AKT on response to therapy. Analysis of these gene signatures identified reveals general modes of action of multicomponent therapies and the mechanisms of specific drug combinations, highlights the potential value of molecular interaction profiles in the discovery of novel therapies, and provides more information for personalized cancer medicine.