NF1 in NSCLC
Research type
Research Study
Full title
Next-Generation Sequencing into practice: Identifying functionally important aberrations in neurofibromin-1 (NF-1) in non-small cell lung cancer (NSCLC)
IRAS ID
165821
Contact name
Sarah Danson
Contact email
Sponsor organisation
Sheffield Teaching Hospitals NHS Trust
Duration of Study in the UK
3 years, 8 months, 26 days
Research summary
Next-Generation Sequencing into practice: Identifying functionally important aberrations in neurofibromin-1 (NF-1) in non-small cell lung cancer (NSCLC)
Lung cancer kills more people than any other cancer and NSCLC is the commonest type of lung cancer. Mainstay treatment options for advanced disease include chemotherapy, which offers limited benefits, or, for a small percentage of patients, new targeted agents offer a better outlook. This percentage could increase with further targeted therapies currently in clinical trials. In order to maximise the benefits these new agents will bring, we need to understand the underlying mechanisms and identify biomarkers which will allow successful stratification and selection of patients.
Neurofibromatosis is a common inherited disorder affecting approximately 1 in 3000 individuals. The disease is the result of mutations in the tumour suppressor gene NF-1. These mutations leave the individual with increased susceptibility to the development of specific benign and malignant tumours. NF-1 functions to inhibit the activation of cellular signalling pathways which are widely associated with cancer. It has recently been observed that sporadic NF-1 mutations can be found in many different cancers. Mutations in NF-1 are observed in 8-12% of NSCLC tumours. Inactivation of NF-1 has already been linked to possible acquired resistance to targeted therapeutics in models for NSCLC. However, a link between mutations found in NF-1 and functional effects on cell signalling pathways is lacking.
This study aims to address this, by conducting genetic analysis of NF-1 mutations and linking these to cell signalling pathway activation, commonly related to NSCLC. Next generation sequencing will enable rapid analysis of NF-1 and further establish this platform as a diagnostic tool. If successful, this could lead to NF-1 status being used as a biomarker to predict response to cancer treatments, such as inhibitors of this pathway that are currently involved in several clinical trials.REC name
Yorkshire & The Humber - Sheffield Research Ethics Committee
REC reference
15/YH/0105
Date of REC Opinion
3 Jun 2015
REC opinion
Further Information Favourable Opinion