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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 | 显示文摘 | Filippi M Martinelli V | 1994 | J Neurol Sci1994，125，： | 1 |
| 3 | Genetic transformation for biotic stress resistance in horticultural plants,in vitro cell显示文摘 | MARTINELLI L RUGINI E SACCADO F | 1996 | Dev Bio Plant1996，32，3： | 1 |
| 4 | Linkage disequilibrium between GABRB3 gene and nonsyndromic familial cleft lip with or without cleft palate显示文摘 | Scapoli L Martinelli M Pezzetti F | 2002 | Hum Genet2002，110，1： | 1 |
| 5 | CamilalCarotid intima-media thickness is associated with cognitivedeficiency in hypertensive patients with elevated central systolicblood pressure 显示文摘 | Dias Eda M Giollo L T Jr Martinelli D D | 2012 | Cardiovascular Ultrasound2012，10，1： | 1 |
| 6 | Nitrogen sta- ble isotopic composition of leaves and soil: Tropical versus tem- perate forests显示文摘 | Martinelli L A Piccolo M C Townsend A R | 1999 | Biogeochemistry1999，46，： | 1 |
| 7 | Strong evidence of linkage disequihbrium between polymorphisms at the IRF6 locus in nonsyndromic cleft lip with or without cleft palate, in a Italian population 显示文摘 | Scapoli L Palmieri A Martinelli M | 2005 | Am J Hum Genet2005，76，1： | 1 |
| 8 | Microarray analysis and RNA silencing link Fra-1 to CD44 and c-met expression in mesothelioma显示文摘 | Ramos-Nino ME Scapoli L Martinelli M | | 0，，13： | 1 |
| 9 | Strong evidence of linkage disequilibrium between polymorphisms at the IRF6 locus and nonsyndromic cleft lip with or without cleft palate,in an Italian population显示文摘 | Scapoli L Palmieri A Martinelli M | 2005 | Am J Hum Genet2005，76，1： | 1 |
| 10 | The use of stable isotopes in studies of nutrient cycling:Carbon isotope composition of Amazon varzea sediments显示文摘 | VICTORIA R L MARTINELLI L A TRIVELIN P C | 1992 | Biotropica1992，24，： | 1 |
| 11 | Somatic Embryogenesis from Leaf and Petiole Derived Callus of gitis rupestris 显示文摘 | MARTINELLI L BRAGAGNA P POLETTI V | 1993 | Plant Cell Reports1993，12，4： | 1 |
| 12 | Worldwide stable carbon and nitrogen isotopes of Big Mac patties: An example of a truly “glocal” food显示文摘 | Martinelli L A Nardoto G B Chesson L A | 2011 | Food Chemistry2011，127，4： | 1 |
| 13 | C667T variant form at the MTHFR gene and CL/P: a risk factor for mothers 显示文摘 | Scapoli L Pezzetti F | 2001 | Am J Med Genet2001，98，4： | 1 |
| 14 | A locus in2p13-p14(OFC2),in addition to that mapped in6p23,is in-volved in nonsyndromic familial orofacial cleft malforma-tion显示文摘 | Pezzetti F Scapoli L Martinelli M | 1998 | Genomics1998，50，3： | 1 |
| 15 | Strong evidence of link- age disequilibrium between polymorphisms at the IRF6 locus in nonsyndromic cleft lip with or without cleft palate,in a Italian population显示文摘 | Scapoli L Palmieri A Martinelli M | 2005 | Am J Hum Genet2005，76，1： | 1 |
| 16 | Dissolution mech- anism of 316L in lead-bismuth eutectie at 500 C显示文摘 | YAMAKI E GINESTAR K and MARTINELLI L | 2001 | Corrosion Sci- ence2001，53，10： | 1 |
| 17 | Nonlinear oscillations of cables under harmonic loading using analytical and finite element models显示文摘 | GATTULLI V MARTINELLI L PEROTTI F | 2004 | Computer Methods in Applied Mechanics and Engineering2004，193，： | 1 |
| 18 | BGK based schemes for the simulation of compressible flow显示文摘 | Xu K Kim C A Martinelli L Jameson A | 1996 | International Journal of Computational Fluid Dynamics1996，7，： | 1 |
| 19 | Effect of land use on water chemistry and macroinvertebrates in two streams of the Piracicaba river basin, south-east Brazil显示文摘 | Ometo J P H B Martinelli L A Ballester M V | 2000 | Freshwater Biology2000，44，： | 1 |
| 20 | Microarray analysis and RNA silencing link fra-1 to cd44 and c-met expression in mesothelioma显示文摘 | Ramos-Nino ME Scapoli L Martinelli M | 2003 | Cancer Res2003，63，35： | 1 |
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