@article{3085719,
    title = "Co-targeting of EGFR and autophagy signaling is an emerging treatment strategy in metastatic colorectal cancer",
    author = "Koustas, E. and Karamouzis, M.V. and Mihailidou, C. and Schizas, D. and Papavassiliou, A.G.",
    journal = "Cancer Letter",
    year = "2017",
    volume = "396",
    pages = "94-102",
    publisher = "Elsevier Ireland Ltd",
    doi = "10.1016/j.canlet.2017.03.023",
    keywords = "antineoplastic agent;  autophagy related protein;  cetuximab;  chloroquine;  epidermal growth factor receptor;  hydroxychloroquine;  mammalian target of rapamycin;  mitogen activated protein kinase;  panitumumab;  phosphatidylinositol 3 kinase;  protein kinase B;  Raf protein;  Ras protein;  antineoplastic agent;  cetuximab;  EGFR protein, human;  epidermal growth factor receptor;  monoclonal antibody;  panitumumab, antineoplastic activity;  apoptosis;  autophagy;  clinical trial (topic);  drug protein binding;  drug receptor binding;  drug targeting;  human;  metastatic colorectal cancer;  overall survival;  progression free survival;  protein degradation;  protein synthesis inhibition;  protein transport;  receptor down regulation;  Short Survey;  signal transduction;  ubiquitination;  antagonists and inhibitors;  Colorectal Neoplasms;  drug effects;  enzymology;  genetic transfection;  metabolism;  metastasis;  molecularly targeted therapy;  pathology, Antibodies, Monoclonal;  Antineoplastic Agents;  Autophagy;  Cetuximab;  Colorectal Neoplasms;  Humans;  Molecular Targeted Therapy;  Neoplasm Metastasis;  Receptor, Epidermal Growth Factor;  Signal Transduction;  Transfection",
    abstract = "The epidermal growth factor receptor (EGFR) and its associated pathway is a critical key regulator of CRC development and progression. The monoclonal antibodies (MoAbs) cetuximab and panitumumab, directed against EGFR, represent a major step forward in the treatment of metastatic colorectal cancer (mCRC), in terms of progression-free survival and overall survival in several clinical trials. However, the activity of anti-EGFR MoAbs appears to be limited to a subset of patients with mCRC. Studies have highlighted that acquired-resistance to anti-EGFR MoAbs biochemically converge into Ras/Raf/Mek/Erk and PI3K/Akt/mTOR pathways. Recent data also suggest that acquired-resistance to anti-EGFR MoAbs is accompanied by inhibition of EGFR internalization, ubiqutinization, degradation and prolonged downregulation. It is well established that autophagy, a self-cannibalization process, is considered to be associated with resistance to the anti-EGFR MoAbs therapy. Additionally, autophagy induced by anti-EGFR MoAbs acts as a protective response in cancer cells. Thus, inhibition of autophagy after treatment with EGFR MoAbs can result in autophagic cell death. A combination therapy comprising of anti-EGFR MoAbs and autophagy inhibitors would represent a multi-pronged approach that could be evolved into an active therapeutic strategy in mCRC patients. © 2017 Elsevier B.V."
}