Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - MELGEN (MELanoma GENetics - understanding and biomarking the genetic and immunological determinants of melanoma survival)

Teaser

The MELGEN European Training Network (ETN) and Consortium was designed as an environment for long-term, collaborative, cancer genetics research with the ultimate aim of improving precision (personalised) medicine. Comprised of 17 PhD early stage researchers (ESRs) and their...

Summary

The MELGEN European Training Network (ETN) and Consortium was designed as an environment for long-term, collaborative, cancer genetics research with the ultimate aim of improving precision (personalised) medicine. Comprised of 17 PhD early stage researchers (ESRs) and their laboratory colleagues, MELGEN is working primarily to understand survival from melanoma skin cancer and response to therapies using a variety of cutting-edge scientific techniques with a focus on genetics and immunity.

MELGEN’s genetic research is focused on determining which genes are mutated (changed) or “expressed” differently in melanomas removed from patients who survived and those who did not. The genetic make-up of a cancer largely determines how the cancer cells behave and finding the genes which are altered tells us something important about that cancer. In parallel MELGEN is also exploring the genes which increase risk of developing melanoma. By combining these approaches MELGEN will better understand the biology of melanoma and therefore explore potential new treatment options.

Research within MELGEN and at other centres has shown that when there is evidence of a strong immune response to their cancer, the patient has a much stronger chance of survival. Some of MELGEN’s focus is therefore specifically about increasing our knowledge about how such immune responses are controlled. By identifying the mechanisms involved MELGEN will increase the likelihood of identifying new drug targets and the development of new treatments.

In order to improve the survival of melanoma patients with advanced disease we have to learn how better to select therapies for patients. A key MELGEN aim is to identify characteristics of the patient and his/her cancer which predict response to a drug. This is often called personalized medicine, and tests which allow medical teams to advise the patient about what treatment is likely to be best for them are called predictive biomarkers. Groups in Leeds, Zurich and Essen are working towards the discovery of such predictive biomarkers.

Work performed

During the first period of the Project, a key aim has been to ensure that the MELGEN consortium maximises the collaborative environment fostered between centres, commercial partners and the ESRs. Network-wide scientific training events, together with complementary skills workshops and scientific meetings at which all students have been encouraged to present to a wider scientific audience, have helped to forge strong bonds of scientific collaboration and friendship between the 17 ESRs.

Local and international outreach and engagement has been actively encouraged with the ESRs contributing regular blog articles to the MELGEN website, visiting schools and public/patient events to talk about their work in MELGEN as well as the wider health implications of sun safety.

During the first two years all the ESRs have made good progress with their projects and many have presented their findings at prestigious international cancer meetings and are in the process of writing up aspects of their research for publication in peer-reviewed journals. A number of ESRs have benefitted from secondments to MELGEN’s commercial partners and other academic centres to widen their knowledge and experience on subjects or skills required for their projects. Those ESRs visiting commercial partners have also had a valuable insight into the realities of working in industry.

Key research performed during this period includes:
a) ESRs at the Sanger, in Leiden and in Norway have worked on finding inherited melanoma susceptibility genes. Extensive exploration of genetic data generated from the blood of individuals in families at increased risk of melanoma has identifies some interesting new candidates for genes predisposing to melanoma. Work is now going on to prove that the genes have an effect on melanoma cells
b) In Oslo two ESRs are using cell lines made from melanoma patient skin cells to explore the function of susceptibility genes. They have focussed on a gene of previously known relevance to melanoma and have exciting new data suggesting a potentially important role for that gene in melanoma progression.
c) ESRs in Leeds and Lund have been using data on how genes are expressed in primary melanoma tumours to identify groups of tumours with signs of different immune responses which also show differences in survival. These ESRs benefit from the opportunity to validate their findings in the other’s data. They are exploring different computer (bioinformatic) methods to develop “true” biomarkers. i.e. tests which will perform well in melanoma patients treated in different countries.
d) In Leeds an ESR is investigating the relationship between vitamin D levels in melanoma patients’ blood and melanoma progression.
e) An ESR in Essen is studying genetic changes in the Interferon-gamma pathway genes that she has found to have a significant negative impact on melanoma patient survival.
f) An ESR in Zurich has identified a potential biomarker which could predict disease progression in patients under treatment using check-point inhibitor therapies. This work is currently under review for publication in a high impact scientific journal.

Final results

MELGEN is providing early stage researchers (ESRs) with the necessary skills to enable European research institutes and Biotech companies to compete internationally, and will therefore enhance the ESRs’ career opportunities, by:
• Giving them access to forefront genomics at the Sanger and partner SME GenomeScan;
• Delivering higher quality statistics and bioinformatics training than would be possible by any one institution, reflecting the current rapid evolution of this aspect of science;
• Promoting access to experience of science processes in the commercial sector;
• Carrying out topical research: being related to immunotherapies and biomarker discovery;
• Fostering cross-fertilisation of research between units in different countries.

In the longer term MELGEN will also benefit the commercial companies, especially with respect to the development of clinical biomarkers, by providing them with academic and clinical partners, as well as providing a pool of recruitable graduates at the end of their training.

The researchers are benefiting from tailored research and complementary training, providing a diverse skill set which has already raised their scientific profile in research workshops, online dissemination and private sector placements. They will gain an advantage over researchers trained in a single institution. Just as importantly, through being exposed to a highly supportive group of researchers who have achieved success through collaboration the ESRs are already coming to understand how a culture of long-term collaboration is crucial to progress and success. Many of the ESRs are already developing into independent researchers with the potential to lead future training and research networks.

MELGEN is strongly patient-oriented and will hopefully lead to future clinical applications. MELGEN’s commercial partners play a vital role in the network’s management, training and research activities. Via placements, technical skills will be transferred between laboratories, and the different methodologies employed by those laboratories will be harmonised, thereby increasing the international competitiveness of participating companies and institutions.

Website & more info

More info: http://www.melgen.org.