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Primary resistance to cetuximab therapy in EGFR FISH-positive colorectal cancer patients

CAPPUZZO, F ; VARELLA-GARCIA, M ; HOLMES, A. J ; TOSCHI, L ; TALLINI, G ; DESTRO, A ; RONCALLI, M ; SANTORO, A ; JÄNNE, P. A ; FINOCCHIARO, G ; SKOKAN, M ; GAJAPATHY, S ; CARNAGHI, C ; RIMASSA, L ; ROSSI, E ; LIGORIO, C ; DI TOMMASO, L

British journal of cancer, 2008-07, Vol.99 (1), p.83-89 [Periódico revisado por pares]

Basingstoke: Nature Publishing Group

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Título:
Primary resistance to cetuximab therapy in EGFR FISH-positive colorectal cancer patients
Autor: CAPPUZZO, F ; VARELLA-GARCIA, M ; HOLMES, A. J ; TOSCHI, L ; TALLINI, G ; DESTRO, A ; RONCALLI, M ; SANTORO, A ; JÄNNE, P. A ; FINOCCHIARO, G ; SKOKAN, M ; GAJAPATHY, S ; CARNAGHI, C ; RIMASSA, L ; ROSSI, E ; LIGORIO, C ; DI TOMMASO, L
Assuntos: Antibodies, Monoclonal - therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic agents ; Antineoplastic Agents - therapeutic use ; Biological and medical sciences ; Cancer research ; Cetuximab ; Clinical Study ; Colorectal cancer ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - genetics ; Drug Resistance, Neoplasm - genetics ; Epidermal growth factor ; Ethanol ; Female ; Gene amplification ; Humans ; Immunotherapy ; In Situ Hybridization, Fluorescence ; Kinases ; Male ; Medical research ; Medical sciences ; Metastasis ; Middle Aged ; Mutation ; Nuclear Proteins - genetics ; Oncology ; Patients ; Pharmacology. Drug treatments ; Proteins ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins B-raf - genetics ; Proto-Oncogene Proteins c-met ; Proto-Oncogene Proteins p21(ras) ; ras Proteins - genetics ; Receptor, Epidermal Growth Factor - genetics ; Receptors, Growth Factor - genetics ; Receptors, Somatomedin - genetics ; Response rates ; Transcription Factors - genetics ; Tumors
É parte de: British journal of cancer, 2008-07, Vol.99 (1), p.83-89
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Descrição: The impact of KRAS mutations on cetuximab sensitivity in epidermal growth factor receptor fluorescence in situ hybridisation-positive (EGFR FISH+) metastatic colorectal cancer patients (mCRC) has not been previously investigated. In the present study, we analysed KRAS, BRAF, PI3KCA, MET, and IGF1R in 85 mCRC treated with cetuximab-based therapy in whom EGFR status was known. KRAS mutations (52.5%) negatively affected response only in EGFR FISH+ patients. EGFR FISH+/KRAS mutated had a significantly lower response rate (P=0.04) than EGFR FISH+/KRAS wild type patients. Four EGFR FISH+ patients with KRAS mutations responded to cetuximab therapy. BRAF was mutated in 5.0% of patients and none responded to the therapy. PI3KCA mutations (17.7%) were not associated to cetuximab sensitivity. Patients overexpressing IGF1R (74.3%) had significantly longer survival than patients with low IGF1R expression (P=0.006), with no difference in response rate. IGF1R gene amplification was not detected, and only two (2.6%) patients, both responders, had MET gene amplification. In conclusion, KRAS mutations are associated with cetuximab failure in EGFR FISH+ mCRC, even if it does not preclude response. The rarity of MET and IGF1R gene amplification suggests a marginal role in primary resistance. The potential prognostic implication of IGF1R expression merits further evaluation.
Editor: Basingstoke: Nature Publishing Group
Idioma: Inglês

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Primary resistance to cetuximab therapy in EGFR FISH-positive colorectal cancer patients

CAPPUZZO, F ; VARELLA-GARCIA, M ; HOLMES, A. J ; TOSCHI, L ; TALLINI, G ; DESTRO, A ; RONCALLI, M ; SANTORO, A ; JÄNNE, P. A ; FINOCCHIARO, G ; SKOKAN, M ; GAJAPATHY, S ; CARNAGHI, C ; RIMASSA, L ; ROSSI, E ; LIGORIO, C ; DI TOMMASO, L

Basingstoke: Nature Publishing Group

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