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Bonin, S; Donada, M; Bussolati, G; Nardon, E; Annaratone, L; Pichler, M; Chiaravalli, AM; Capella, C; Hoefler, G; Stanta, G.
A synonymous EGFR polymorphism predicting responsiveness to anti-EGFR therapy in metastatic colorectal cancer patients.
Tumour Biol. 2016; 37(6):7295-7303
Web of Science PubMed FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Hoefler Gerald
Pichler Martin
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Abstract:
Genetic factors are known to affect the efficiency of therapy with monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor (EGFR) in patients with metastatic colorectal cancer (mCRC). At present, the only accepted molecular marker predictive of the response to anti-EGFR mAbs is the somatic mutation of KRAS and NRAS as a marker of resistance to anti-EGFR. However, only a fraction of KRAS wild-type patients benefit from that treatment. In this study, we show that the EGFR gene polymorphism rs1050171 defines, independently of RAS mutational status, a sub-population of 11 % of patients with a better clinical outcome after anti-EGFR treatment. Median PFS for patients with the GG genotype was 10.17 months compared to 5.37 of those with AG + AA genotypes. Taken together, our findings could be used to better define CRC populations responding to anti-EGFR therapy. Further studies in larger independent cohorts are necessary to validate the present observation that a synonymous polymorphism in EGFR gene impacts on clinical responsiveness.
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Adenocarcinoma - drug therapy
Adenocarcinoma - genetics
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Aged -
Antibodies, Monoclonal - therapeutic use
Antineoplastic Agents - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Camptothecin - administration & dosage
Camptothecin - analogs & derivatives
Cetuximab - administration & dosage
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Colorectal Neoplasms - drug therapy
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Disease-Free Survival -
Drug Resistance, Neoplasm - genetics
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Genes, erbB-1 -
Genes, ras -
Humans -
Irinotecan -
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Proto-Oncogene Proteins p21(ras) - genetics
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Find related publications in this database (Keywords)
mCRC
RAS mutation
EGFR gene polymorphism rs1050171
Synonymous SNP
FFPE
Survival
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