Imperial Mucosal Melanoma Characterization (IMMC)
Research type
Research Study
Full title
Identifying novel therapeutic targets and biomarkers in mucosal melanoma
IRAS ID
251375
Contact name
Nelofer Syed
Contact email
Sponsor organisation
Imperial College London
Duration of Study in the UK
4 years, 0 months, 30 days
Research summary
Mucosal melanoma is a rare and aggressive subset of melanoma, accounting for approximately 1% of all USA melanoma diagnoses. There are limited therapies available for this disease and as such 5-year survival is just 25%.
A few specific treatments trialed for mucosal melanoma have shown promise, however due to their targeted nature, the development of drug resistance is inevitable and fast. Additionally, the mutational landscape of the disease is poorly defined. The few papers that highlight important mutational signatures conflict with each other in their findings, suggesting our understanding to be incomplete. One reason for the lack of data in this field of study is the limited availability of mucosal melanoma models - no commercially available cell lines exist so research is limited to the availability of primary tissue or retrospective patient data analysis, which again is very difficult to obtain.As such, our primary aim is to use deep sequencing to validate known mutational signatures and identify novel mutational signatures of the disease. We then plan to explore if these mutations can be targeted for novel therapy. This will involve extracting DNA and RNA from the archival tissue collected from Broomfield Hospital (MEHT), and performing Next Generation Sequencing on this tissue. In moving forward, we aim to collect fresh tissue and establish better models of mucosal melanoma disease by culturing primary cell lines derived from patients. With this tissue, further functional analysis is carried out to validate the efficacy of targeting the novel mutational signatures identified in the deep sequencing. This will involve chemically and biologically blocking the identified novel targets, and analysing the resultant changes in cancer growth, invasion and various other characteristics of aggression. We hypothesise that blocking the identified mutational signatures of the disease we can reduce the pathogenesis, and hence this marks potential as a therapeutic.
Results Summary
: Melanoma encompasses a number of malignancies all originating from cells of melanocytic origin. Generally speaking, melanoma has a promising prognosis with a five-year survival rate of 91.3%, however two subtypes in particular – melanoma brain metastasis (MBM) and mucosal melanoma (MM) – have a high mortality and limited therapeutic options. Cancerous cells frequently have altered metabolic pathways in order to sustain their rapid growth. Melanoma of the skin has previously been shown to respond to a therapy that relies on the removal of a semi essential nutrient, arginine (arginine deprivation therapy). However, to date MBM have been excluded from such trials.This study aimed to explore if MBM and MM would respond to arginine deprivation therapy and moreover, it aimed to identify additional therapeutic options by detailed analysis of the tumour samples using novel technologies.
REC name
North West - Greater Manchester South Research Ethics Committee
REC reference
19/NW/0200
Date of REC Opinion
29 Apr 2019
REC opinion
Further Information Favourable Opinion