Project Interview: Exploiting MELanoma disease comPLEXity – MEL-PLEX

What are general and long term goals of the project?
In the absence of personalised and optimised treatment options, great numbers of cancer patients suffer from inefficient therapies. Malignant melanoma exemplifies a largely chemotherapy-resistant, highly heterogeneous and aggressive cancer. Novel treatment options for personalised, patient-tailored melanoma therapies can now be explored or developed through newly emerging and innovative research disciplines that go significantly beyond the current state-of-the-art, such as translational cancer systems biology and cancer systems medicine. MEL-PLEX is a European Training Network currently training 15 Early Stage Researchers in these disciplines by investigating the network-level and multi-scale regulation of disease relevant signalling in melanoma. The MEL-PLEX research training programme includes partners from European and international academic/clinical and private sector leaders in personalised melanoma therapy, melanoma systems biology and cancer systems medicine. MEL-PLEX addresses current needs in academia and the private sector for researchers that have been interdisciplinarily trained, that can navigate confidently between clinical, academic and private sector research environments, and that have developed an innovative and creative mindset to progress research findings towards applications.

Please state a few more specific objectives of the project.
The main goals of the MEL-PLEX project are:

  1. to achieve an unmatched depth of molecular and mechanistic disease understanding,
  2. to exploit this knowledge to develop and validate predictive models for disease progression, prognosis and responsiveness to current and novel (co-)treatment options, and
  3. to provide superior and clinically relevant tools and biomarker signatures for personalising and optimising melanoma therapy.

Describe the methodology, approach and technologies used.
MEL-PLEX investigates disease-relevant signalling networks (programmed cell death, autophagy, survival/proliferation signalling and immune responses), their interactions, their pathological perturbations, and their key regulatory genes and proteins. This will allow the consortium to address current unmet needs in the field of melanoma research and development, and to provide innovative systems biological and systems medical solutions that promote the rational design of optimal patient surveillance and treatment strategies. MEL-PLEX unites multiple disciplines, such as mathematical modelling, systems theory, cancer cell biology, pharmacology, human physiology, and medicine, thereby providing the foundation for a comprehensive research strategy in translational systems biology and systems medicine that goes significantly beyond the current state-of-the-art. The programme is divided into two research & development work packages comprising the early stage researchers’ individual projects, each of which is addressed through intersectoral and interdisciplinary research in which individual researchers conduct both experimental and mathematical modelling work in both academic and private sector environments. The first work package, MEL-TARGET, aims to decipher the complex signalling systems triggered and perturbed by novel targeted therapeutics in order to develop prototype systems models with can predict responsiveness and which can serve as innovative patient stratification and treatment decision tools. The second, MEL-MARK, aims to evaluate control features and signalling nodes in known disease relevant pathways as novel prognostic and predictive combinatorial systems biomarkers for melanomagenesis, progression, and (co-)treatment responsiveness.

How is the project progressing, any results you wish to highlight?
MEL-PLEX has just started its second year with a very positive balance so far. The consortium achieved its main milestone of recruiting 15 excellent early stage researchers after a highly competitive call which attracted over 400 very talented young researchers worldwide. Although only in the first 6-8 months of their PhD projects, MEL-PLEX early stage researchers have already presented their work in 11 national and international meetings and have submitted one original paper and one review article for publication. The innovativeness of the programme has attracted the keen interest of the Research Executive Agency who invited MEL-PLEX representatives to talk more about the programme during the EU Presidency conference “Future of the Doctorate” held in Riga, Latvia last May and we were also invited to discuss our strategies at the CASyM/SysMedIBD workshop in Brussels next February. Through the MEL-PLEX consortium, its partners have successfully secured new high profile funding awards, such as another Marie Skłodowska Curie Actions European Training Network, H2020 Small and Medium-sized Enterprise Instrument funding, and EU Cooperation in Science and Technology (COST) Actions.

Funding source and funding duration:
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 642295. Start date: December/2014, End date: November/2018 (48 months).

Isabela Aparicio