Periodic Reporting for period 2 - ALKATRAS (ALK Activation as a target of TRAanslational Science (ALKATRAS): Break free from cancer)
Okres sprawozdawczy: 2017-09-01 do 2019-08-31
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
In achieving these aims, we have conducted research that has highlighted the mechanisms of tumour development as they relate to aberrant expression of the ALK protein resulting in multiple research papers published in open access journals as well as review articles which are of great benefit to the academic and clinical research communities to assist in teaching, training and improving general understanding of tumorigenic processes. We have also successfully trained 15 early stage researchers who will be able to move on in their careers to disseminate their research findings and contribute to society by continuing to work in this or a related field. The early stage researchers were recruited from all over the world and conducted research in a lab in a different country to their own facilitating cross-cultural interactions. All of the researchers also spent time in industry as well as another academic lab developing networks of peers and colleagues. The network will continue to work together into the future to address the clinical problem that is improving the survival and treatment outcome of patients with ALK-expressing malignancies.
The 4 scientific work packages (wp) led to the production of interesting and informative research data with the 15 ESR having worked 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 have been explored. Under wp3, novel therapeutic approaches were explored ranging from tumour vaccination through to combinatorial activities of novel targeted agents. 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 further investigation. We have also developed a commercial assay to detect circulating antibodies to ALK in patient's peripheral blood in collaboration with our partner organisation Cambridge Life Sciences. Additionally, the effects of co-treatment of ALCL with immune checkpoint inhibitors and ALK inhibitors has been investigated with promising results of relevance to the future treatment of patients. Finally, in wp4, the novel ALK inhibitor TPX-0005 has been assessed for its ability to inhibit the growth of ALK-addicted neuroblastoma cell lines and this activity will continue to determine its effects against numerous mutant forms of ALK.
Overall, the ALKATRAS project has fulfilled its aims and goals not only having trained 15 ESR but also producing important research findings with clinical applications and disseminating this research to both professional and lay audiences.