Metabolic Phenotypes in Melanoma

Identification of Metabolic Phenotypes Associated With Prognosis and Therapeutic Response in Patients With Melanoma

This is a single centre, correlative, longitudinal, biomarker study that aims to describe the metabolic features of human melanoma using mass spectrometry.

This is a single-centre, correlative study designed to investigate metabolic phenotypes in a longitudinal cohort of patients with melanoma. This study will involve the collection of tissue at the time of surgical excision or biopsy. The key intervention, in a subset of patients, will be to perform peri-operative infusions of a stable isotope, [U13C]Glucose. Patients will be intravenously administered sterile, pyrogen-free 13C-glucose, delivered as an 8g bolus followed by infusion of 4g/hour for 2-3 hours. Blood samples will be obtained to monitor glucose and to analyse enrichment of labelled nutrients by gas-chromatography mass spectrometry (GC-MS). At the time of resection or biopsy, tumour samples will be divided and either immediately frozen in liquid nitrogen or processed to form patient-derived xenografts. Frozen tumour samples will be subsequently processed for: isotope enrichment by GC-MS; global metabolomics by liquid-chromatography mass spectrometry (LC-MS); and genomic analyses. Relevant clinical, histologic and genomic features will also be correlated with metabolic findings.

Inclusion Criteria:

1. Patient has provided written informed consent
2. Male or female aged 18 years or older at written informed consent
3. Presence of a known melanoma lesion requiring surgical excision or biopsy
4. Patient is willing and able to comply with the protocol for the duration of the study including undergoing biopsies and receiving a stable isotope infusion (where applicable)

Exclusion Criteria:

Patients who meet any of the following criteria will be excluded from receiving a [U-13C]Glucose infusion:

1. Diabetes mellitus
2. Pregnancy or breast feeding
3. Patients unable to comply with study procedures and follow up in the opinion of the investigator