Identifying novel solutions to BRAF inhibitor resistance in melanomaV7
Research type
Research Study
Full title
Identifying novel solutions to BRAF inhibitor resistance in melanoma Assessment of markers in matched melanoma samples
IRAS ID
225135
Contact name
Rowan Pritchard Jones
Contact email
Sponsor organisation
St Helen's & Knowsley NHS Trust
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Malignant melanoma is the most deadly of the skin cancers we manage.
There are 10,000 new cases every year in the UK, and here in Liverpool we treat more patients than any other UK unit.
Until recently, patients developing advanced melanoma had few choices. The development of the BRAF inhibitors has changed that. Some 60% of patients have a genetic change in their melanoma that makes their disease highly sensitive to the drug. There is a rapid shrinkage of disease within days of starting treatment. However, the effect of this drug lasts only 6 to 9 months as patients go on to develop resistance. The reason for this lies in residual melanoma cells that mutate to open up new growth pathways, untouched by the drug, and rapidly grow once more. We have already described some of these mechanisms by growing and analysing vemurafenib resistant cells in the laboratory. We have found that some of the changes in these cells makes them MORE susceptible to some well known chemotherapy medicines, but interestingly not routinely used for melanoma. With this project we hope to confirm these findings in different cell types collected from our patients, and provide the evidence to develop trials of existing medicines when BRAF inhibitor resistance emerges.
The study involves collecting melanoma cells from patients with advanced disease following testing for the genetic changes ensuring suitability for a BRAF inhibitor, and before commencing treatment. Cells extracted from this process will be stored and analysed. Following treatment with the drug, all patients become resistant and often return to their surgeon to remove disease in order to palliate symptoms. At this point we will have matched tumour cells to look at genetic characteristics before and after treatment.
Patients will be recruited in Whiston Hospital and their tissue stored and analysed at Liverpool University.REC name
North West - Liverpool Central Research Ethics Committee
REC reference
17/NW/0387
Date of REC Opinion
21 Aug 2017
REC opinion
Further Information Favourable Opinion