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Molecular Dissection of Melanoma Progression: An integrated Pan-European Approach

Final Report Summary - TARGET-MELANOMA (Molecular Dissection of Melanoma Progression: An integrated Pan-European Approach)


Executive Summary:

Malignant melanoma is a highly aggressive disease, with minimal treatment options for patients that present in the later stages. Melanoma cells use several strategies to enable their progression to advanced melanoma and metastasis, including genetic and epigenetic alterations, along with disruptions to gene and protein expression. In our Industry-Academia Partnerships and Pathways (IAPP) programme, Target-Melanoma, we investigated the molecular basis underlying this difficult-to-treat disease, focusing on the discovery of new biomarkers (i.e. indicators) for predicting the progression of melanoma or potential targets for therapy.

Target-Melanoma (www.targetmelanoma.com) was a collaborative effort undertaken by 7 partners across 5 EU countries, including 5 academic institutions and 2 SMEs. This pan-European project, with a total budget of just over €1.75M encouraged cooperation between key academic and industrial partners, centred on the intersectorial training of experienced researchers who were recruited by or seconded between institutions. A total of 13 recruitments and secondments were completed during the course of the programme.

The aim of the Target-Melanoma programme was to investigate several areas of melanoma biology, taking advantage of a variety of advanced biomedical research technologies in this context. Specifically, several of our academic groups brought expertise in relation to the study of melanoma progression and epigenetic mechanisms. In addition, they provided access to hundreds of tumour samples, which are difficult to obtain, and were used throughout the project. The two SMEs involved provided access to and training in state-of-the-art technologies, and this project allowed them to expand into the cancer/melanoma area, as well as to develop new products.

The Target-Melanoma collaborative effort identified a wide selection of potential melanoma biomarkers using both in-house discovery approaches and re-analysis of pre-existing omic-level data. A subset of these biomarkers was extensively validated using melanoma tissue cohorts available to the consortium. In more detail, Illumina arrays, pyrosequencing and in silico analysis were utilised to identify methylated genes in cell lines and tissues. In addition, investigations were made into the associations between melanoma progression and prognosis, and expression of these methylated genes, or other potential biomarkers. For this aspect of the project, a key focus was the application of tissue microarray technology and associated image analysis approaches. Prioritised targets were functionally validated by a unique in vitro assay that models extravasation, or exit of cancer cells out of the blood stream, a key step in the metastatic process. Separate analysis of melanoma tissues by high-throughput genotyping revealed unexpected mutation rates in melanoma-associated genes in the Irish population, which will be further validated in future studies. These findings could potentially impact the treatment of certain melanoma patient groups, and further confirm the need for additional melanoma biomarkers and therapy targets.

Overall, these studies further elucidated the process of melanoma progression, and identified potential targets for melanoma treatment. In addition, this industry-academic partnership provided a valuable cross-disciplinary training ground for emerging researchers.