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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - ALKATRAS (ALK Activation as a target of TRAanslational Science (ALKATRAS): Break free from cancer)

Teaser

Summary

The objectives of ERIA (The European Research Initiative for ALK-Related Malignancies) as a network of scientists across Europe, is to coordinate and conduct multidisciplinary research efforts into Anaplastic Lymphoma Kinase (ALK)-driven cancers predominantly Anaplastic Large Cell Lymphoma (ALCL) and neuroblastoma â€“ both being largely paediatric malignancies. Embedded into this established international research network, the ALKATRAS programme was developed to:

1- nurture and provide an excellent training environment to a cohort of 15 Early Stage Researchers (ESRs) to become confident, competent, independent and well-connected European scientists

2- facilitate research into ALK-related malignancies with the aim of informing more efficient, less toxic therapies

3- encourage networking across Europe of all parties with an interest in paediatric ALK-related cancers and to widen the net of our public outreach.

4- provide a focused platform for data presentation and discussion of latest advances, research findings related to ALK-induced cancers, specifically neuroblastoma and lymphoma

Work performed

ALKATRAS is composed of 7 work packages (wp) with wp1-4 covering the scientific goals of the programme, wp5 for management, wp6 for training and wp7 for dissemination and outreach. Work has commenced within all of these work packages with considerable progress already achieved even though most ESR have only been in position for 1 year (year 2 of the programme). In the first year, the large majority of time was spent on wp5 whereby procedures were put in place for the recruitment of 15 ESR and management of the programme; we have recruited 15 ESR from across the World into our laboratories to conduct cutting edge research. These students come from a variety of countries ranging from Mexico to India, are two thirds female and are all within the first 4 years of their research careers. In order to facilitate management of ALKATRAS, we have also recruited a project manager who is responsible for organisation and administration tasks, and has made significant progress in putting in place a management structure starting with the supervisory board consisting of a representative from each beneficiary, partner organisation and 2 ESR, the research board with members representing each of the scientific work packages as well as ESR and the coordinator, the training committee, the ESR committee and the scientific advisory board. All boards and committees have met in person at least twice so far with Skype and teleconferences conducted as required. Within wp6, a training programme has been developed consisting of compulsory and optional network-wide elements as well as local training events and secondments. To date, 2 secondments have been conducted, one in an industrial setting and the other in an academic lab; the remaining secondments (2 per student - 1 in academia and 1 in industry) will be conducted over the course of the next 2 years of the programme. We have also completed 3 of the compulsory training events with a workshop on epigenetics held in Vienna, a course on genome analysis in Brno and a workshop with the Naked Scientists in Cambridge. All of the courses received excellent feedback from the students and we look forward to the remaining 4 events that will take place over the next 2 years. All of our ESR have also attended multiple local training activities ranging from lab health and safety to specific training in techniques and all of these are detailed in their personal career and development plans. Dissemination and outreach activities conducted under wp7 have also been a great success with many of our students having communicated their research activities through poster presentations at multiple conferences as well as via social media, in particular podcasts published on the ALKATRAS and Naked Scientists websites as well as blogs. We are also in the process of preparing a whole issue of the journal \'Cancers\' by writing a series of review articles in collaboration with one another to disseminate our research activities to a wider audience. Whilst no original research articles have been published to date, there are at least 2 papers at differing stages of the publication process and undoubtedly more will follow in time.

The 4 scientific work packages are underway with the 15 ESR all working on different aspects ranging from understanding fundamental biological mechanisms of Anaplastic Lymphoma Kinase (ALK)-induced lymphomagenesis (wp1) through to mechanisms of disease resistance (wp4). Specifically, within wp1 and 2 both genetic and epigenetic events as a consequence of aberrant ALK activity are being explored analysing the functional roles of miRNAs, histone modifying proteins and transcription factors in tumorigenesis. Under wp3, novel therapeutic approaches are being explored ranging from tumour vaccination through to combinatorial activities of novel targeted agents. So far, it has been possible to show that children with ALCL develop a CD4+ T cell specific immune response to ALK and the mechanisms of this are under fu

Final results

The Early Stage Researchers (ESR) of the ALKATRAS programme have been in position for approximately 1 year to date but have still made significant progress in their research activities and have developed promising data for further exploration. In particular, our combined research activities involving representatives from paediatric and adult oncology, fundamental scientists and industry are together making significant progress in furthering our understanding of cancers driven by the aberrant expression of a protein called Anaplastic Lymphoma Kinase (ALK). In particular, as well as improving our understanding of the mechanisms of these diseases, we are making significant headway in developing novel therapeutics and disease biomarkers that will inform on the future management of these patients, a process aided by the inclusion of clinical oncologists holding key positions in clinical trial groups within Europe. Of note, a commercial assay has been developed to detect circulating ALK antibodies in patient serum which will be applied to the management of patients as a predictive test for treatment outcome that may facilitate the use of less toxic regimens; final stages of validation are currently underway. In addition, we are currently evaluating novel ALK inhibitors for their efficacy in the treatment of both naive and relapsed disease. As such, by the end of the programme we will have not only improved our understanding of how these diseases develop and occur but also better ways the treat them both at initial presentation and on relapse.