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| 1 | Mechanisms of resistance to anti-epidermal growth factor receptor inhibitors in metastatic colorectal cancer显示文摘The prognosis of patients with metastatic colorectal cancer(m CRC) remain poor despite the impressive improvement of treatments observed over the last 20 years that led to an increase in median overall survival from 6 mo, with the only best supportive care, to approximately 30 mo with the introduction of active chemotherapy drugs and targeted agents. The monoclonal antibodies(mo Abs) cetuximab and panitumumab, directed against the epidermal growth factor receptor(EGFR), undoubtedly represent a major step forward in the treatment of m CRC, given the relevant efficacy in terms of progression-free survival, overall survival, response rate, and quality of life observed in several phase Ⅲ clinical trials among different lines of treatment. However, the anti-EGFR mo Abs were shown only to be effective in a subset of patients. For instance, KRAS and NRAS mutations have been identified as biomarkers of resistance to these drugs, improving the selection of patients who might derive a benefit from these treatments. Nevertheless, several other alterations might affect the response to these drugs, and unfortunately, even the responders eventually become resistant by developing secondary(or acquired) resistance in approximately 13-18 mo. Several studies highlighted that the landscape of responsible alterations of both primary and acquired resistance to anti-EGFR drugs biochemically converge into MEK-ERK and PIK3CA-AKT pathways. In this review, we describe the currently known mechanisms of primary and acquired resistance to anti-EGFR mo Abs together with the various strategies evaluated to prevent, overcame or revert them. | Vincenzo Sforza Erika Martinelli Fortunato Ciardiello Valentina Gambardella Stefania Napolitano Giulia Martini Carminia della Corte Claudia Cardone Marianna L Ferrara Alfonso Reginelli Giuseppina Liguori Giulio Belli Teresa Troiani | 2016 | World Journal of Gastroenterology2016，22，28： | 6 |
| 2 | Why and how do plants cells sense sugars 显示文摘 | Loreti E De Bellis L Alpi A Perata P | 2001 | Ann Bot2001，88，： | 1 |
| 3 | Diagnosis, management and treatment of hepatitis C显示文摘 | Puoti C Guarisco R Bellis L | 2009 | Hepatology2009，50，1： | 1 |
| 4 | Hyperthermia enhances cytotoxicity of amine oxidase and spermine on drugresistance LoVo colon adenocarcinoma cells显示文摘 | Agostinelli E Belli F Dalla Vedova L | | 0，，06： | 1 |
| 5 | Molecular characterization of an Arabidopsis acyl - coenzyme a synthetase localized on glyoxysomal membranes 显示文摘 | Hayashi H De Bellis L Hayashi Y | 2002 | Plant Physiol2002，130，4： | 1 |
| 6 | Elevated 8-isoprostane levels in basal cell carcinoma and in UVA irradiated skin显示文摘 | Belli R Amerio P Brunetti L | 2005 | Int J Immunopathol Pharmacol2005，18，3： | 1 |
| 7 | Arteritis following intra-arterial chemotherapy for liver tumors显示文摘 | Belli L Magistretti G Puricelli GP | 1997 | Eur Radiol1997，7，： | 1 |
| 8 | Transaortic closure of residual intramutal ventricular septal defect显示文摘 | Belli E Houyel L Serraf A | 2000 | Ann Thorac Surg2000，69，5： | 1 |
| 9 | Why and how do plant cells sense sugars显示文摘 | LORETI E BELLIS L D ALPI A | 2001 | Ann Bot2001，，88： | 1 |
| 10 | Phase Ⅰ~Ⅱ trial of Paclitaxel(taxol) and cisplatin in previously untreated advanced nonsmall cell lung cancer (NSCLC)显示文摘 | Le Chevalier T Gottfried M | 1995 | Proc Am Soc Clin Oncol1995，14，： | 1 |
| 11 | Diagnosis, management, and treatment of hepatitis C 显示文摘 | Puoti C Guarisco R Bellis L | 2009 | Hepatology2009，50，1： | 1 |
| 12 | Extrahepatic portal obstruction: Clinical experience and surgical treatment in 105 patients显示文摘 | Belli L Puttini M Marni A | 1980 | J Cardiovasc Surg (Torino)1980，21，4： | 1 |
| 13 | Diagnosis, manage- men, and treatment of hepatitis C显示文摘 | Puoti C Guarisco R Bellis L | 2009 | Hepatology2009，50，1： | 1 |
| 14 | Adoptive immunotherapy of advanced melanoma patients with interleukin-2 (IL-2) and tumor-infiltrating lymphocytes selected in vitro with low doses of IL-2显示文摘 | Arienti F Belli F Rivoltini L | 1993 | Cancer Immunol Immunother1993，36，5： | 1 |
| 15 | Effects of aging and gender on interhemis- pheric function显示文摘 | Bellis T J Wilber L A | 2001 | Journal of Speech Language and Hearing Re- search2001，44，2： | 1 |
| 16 | Which is the best technique for pancreaticoenterie reconstruction after pancreaticoduodenectomy? A critical analysis显示文摘 | Fernandez-Cruz L Belli A Acosta M | | 0，，： | 1 |
| 17 | Diagnosis, manage-ment, and treatment of hepatitis C 显示文摘 | Puoti C Guarisco R Bellis L | 2009 | Hepatology2009，50，1： | 1 |
| 18 | A molecular genetic approach for forensic animal species identification显示文摘 | Bellis C Ashton KJ Freney L | 2003 | Forensic Sci Int2003，，134： | 1 |
| 19 | Characterization of tyrosine phosphorylation of paxillin in vitro by focal adhesion kinase 显示文摘 | Bellis S L Miller J T Tumer C E | 1995 | J Biol Chem1995，270，17： | 1 |
| 20 | A molecular genetic approach for forensic animal species Identification显示文摘 | Bellis C Ashton KJ Freney L | 2003 | Forensic Science International2003，134，： | 1 |
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