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

SUBMITTER: Chaudary N 

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

REPOSITORIES: biostudies-literature