Hedgehog inhibition enhances efficacy of radiation and cisplatin in orthotopic cervical cancer xenografts.
Br J Cancer
; 116(1): 50-57, 2017 01 03.
Article
em En
| MEDLINE
| ID: mdl-27875522
ABSTRACT
BACKGROUND:
The Hedgehog (Hh) pathway is upregulated in cervical cancer and associated with poor outcome. We explored the effects of Hh pathway inhibition in combination with RTCT in a patient derived orthotopic cervical cancer xenograft model (OCICx).METHODS:
5E1, a monoclonal antibody for SHH, or Sonidegib (LDE225), a clinical SMO inhibitor (Novartis) were added to RTCT. We investigated tumour growth delay, metastasis and GI toxicity using orthotopic cervical cancer xenografts models. The xenografts were treated with radiotherapy (15 × 2 Gy daily fractions over 3 weeks) and weekly cisplatin 4 mg kg-1 concurrently, with or without 5E1 or Sonidegib (LDE225). The Hh inhibitors were administered by subcutaneous injection (5E1; 20 mg kg-1 weekly for 3 weeks), or by oral gavage (Sonidegib; 60 mg kg-1 daily for 3 weeks).RESULTS:
We observed that both Hh inhibitors administered with RTCT were well tolerated and showed increased tumour growth delay, and reduced metastasis, with no increase in acute GI-toxicity relative to RTCT alone.CONCLUSIONS:
Our data suggest Hh can be a valid therapeutic target in cervical cancer and supports data suggesting a potential therapeutic role for targeting Hh in patients undergoing RTCT. This warrants further investigation in clinical trials.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Radiossensibilizantes
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Protocolos de Quimioterapia Combinada Antineoplásica
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Neoplasias do Colo do Útero
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Cisplatino
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Proteínas Hedgehog
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Br J Cancer
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Canadá