EGFR-amplification plus gene expression profiling predicts response to combined radiotherapy with EGFR-inhibition: A preclinical trial in 10 HNSCC-tumour-xenograft models.
Radiother Oncol
; 124(3): 496-503, 2017 09.
Article
em En
| MEDLINE
| ID: mdl-28807520
ABSTRACT
BACKGROUND AND PURPOSE:
Improvement of the results of radiotherapy by EGFR inhibitors is modest, suggesting significant intertumoural heterogeneity of response. To identify potential biomarkers, a preclinical trial was performed on ten different human squamous cell carcinoma xenografts of the head and neck (HNSCC) studying in vivo and ex vivo the effect of fractionated irradiation and EGFR inhibition. Local tumour control and tumour growth delay were correlated with potential biomarkers, e.g. EGFR gene amplification and radioresponse-associated gene expression profiles. MATERIAL ANDMETHODS:
Local tumour control 120days after end of irradiation was determined for fractionated radiotherapy alone (30f, 6weeks) or after simultaneous EGFR-inhibition with cetuximab. The EGFR gene amplification status was determined using FISH. Gene expression analyses were performed using an in-house gene panel.RESULTS:
Six out of 10 investigated tumour models showed a significant increase in local tumour control for the combined treatment of cetuximab and fractionated radiotherapy compared to irradiation alone. For 3 of the 6 responding tumour models, an amplification of the EGFR gene could be demonstrated. Gene expression profiling of untreated tumours revealed significant differences between amplified and non-amplified tumours as well as between responder and non-responder tumours to combined radiotherapy and cetuximab.CONCLUSION:
The EGFR amplification status, in combination with gene expression profiling, may serve as a predictive biomarker for personalized interventional strategies regarding combined treatment of cetuximab and fractionated radiotherapy and should, as a next step, be clinically validated.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Escamosas
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Amplificação de Genes
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Perfilação da Expressão Gênica
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Receptores ErbB
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Cetuximab
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Neoplasias de Cabeça e Pescoço
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Antineoplásicos
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Radiother Oncol
Ano de publicação:
2017
Tipo de documento:
Article