التفاصيل البيبلوغرافية
| العنوان: |
Mitogen-activated protein kinase phosphatase-1 (MKP-1) impairs the response to anti-epidermal growth factor receptor (EGFR) antibody cetuximab in metastatic colorectal cancer patients. |
| المؤلفون: |
Montagut, C., Iglesias, M., Arumi, M., Bellosillo, B., Gallen, M., Martinez-Fernandez, A., Martinez-Aviles, L., Cañadas, I., Dalmases, A., Moragon, E., Lema, L., Serrano, S., Rovira, A., Rojo, F., Bellmunt, J., Albanell, J., Cañadas, I |
| المصدر: |
British Journal of Cancer; 3/30/2010, Vol. 102 Issue 7, p1137-1144, 8p, 1 Chart, 3 Graphs |
| مصطلحات موضوعية: |
MITOGEN-activated protein kinases, PHOSPHATASES, EPIDERMAL growth factor, CETUXIMAB, COLON cancer, ANTINEOPLASTIC agents, THERAPEUTIC use of monoclonal antibodies, PROTEIN metabolism, COLON tumors, COMPARATIVE studies, DRUG resistance in cancer cells, RESEARCH methodology, MEDICAL cooperation, METASTASIS, MONOCLONAL antibodies, GENETIC mutation, PROTEINS, RECTUM tumors, RESEARCH, TRANSFERASES, EVALUATION research, CHEMICAL inhibitors |
| مستخلص: |
Background: The validation of KRAS mutations as a negative marker of response to anti-epidermal growth factor receptor (EGFR) antibodies has meant a seminal advance towards treatment individualisation of colorectal cancer (CRC) patients. However, as a KRAS wild-type status does not guarantee a response to anti-EGFR antibodies, a current challenge is the identification of other biomarkers of response. On the basis of pre-clinical evidence, we hypothesised that mitogen-activated protein kinase phosphatase-1 (MKP-1), a phosphatase that inactivates MAPKs, could be a mediator of resistance to anti-EGFR antibodies.Methods: Tumour specimens from 48 metastatic CRC patients treated with cetuximab-based chemotherapy were evaluated for KRAS and BRAF mutational status and MKP-1 expression as assessed by immunohistochemistry.Results: As expected, clinical benefit was confined to wild-type KRAS and BRAF patients. Mitogen-activated protein kinase phosphatase-1 was overexpressed in 16 patients (33%) and was not associated with patient baseline clinicopathological characteristics and KRAS mutational status. All patients with BRAF mutations (n=3) had MKP-1 overexpression. Among KRAS wild-type patients, MKP-1 overexpressors had a 7% response rate (RR), whereas patients not overexpressing MKP-1 had a 44% RR (P=0.03). Moreover, median time to progression was significantly longer in MKP-1 non-overexpressing patients (32 vs 13 weeks, P=0.009).Conclusion: These results support the concept of MKP-1 as a promising negative marker of response to cetuximab-based treatment in CRC patients with wild-type KRAS. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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