Dataset Information

Hedgehog inhibition enhances efficacy of radiation and cisplatin in orthotopic cervical cancer xenografts.

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.

SUBMITTER: Chaudary N

PROVIDER: S-EPMC5220149 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Publications

Hedgehog inhibition enhances efficacy of radiation and cisplatin in orthotopic cervical cancer xenografts.

Chaudary Naz N Pintilie Melania M Hedley David D Hill Richard P RP Milosevic Michael M Mackay Helen H

British journal of cancer 20161122 1

<h4>Background</h4>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).<h4>Methods</h4>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 mo ...[more]

PMID: 27875522

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Dataset Information

Hedgehog inhibition enhances efficacy of radiation and cisplatin in orthotopic cervical cancer xenografts.

Background

Methods

Results

Conclusions

Publications

Hedgehog inhibition enhances efficacy of radiation and cisplatin in orthotopic cervical cancer xenografts.

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