Τίτλος:
Co-targeting of EGFR and autophagy signaling is an emerging treatment strategy in metastatic colorectal cancer
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Koustas, E.
Karamouzis, M.V.
Mihailidou, C.
Schizas, D.
Papavassiliou, A.G.
Εκδότης:
Elsevier Ireland Ltd
Λέξεις-κλειδιά:
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
DOI:
10.1016/j.canlet.2017.03.023
