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Final Report Summary - EUROCSCTRAINING (EUROCANCER STEMCELL TRAINING NETWORK)

Objectives

EuroCancer Stem Cell Training (EuroCSCTraining) Marie Curie Initial Training Network was funded by the 7th Framework Program to provide a unique European training platform for young researchers in the novel field of cancer initiation and in the concept of cancer stem cells to prepare them for a future career in academia, health or industry as well as to provide future research laboratories and industrial partners in Europe with the best qualified researchers.

The recent identification of tumor initiating cells (TIC) or cancer stem cells (CSC) has opened a new area of research for scientists interested in cancer. Understanding the biology of cancer stem cells or initiating cells has already unraveled pathways and potential targets but has also modified our understanding of oncogenesis. Accumulating data in this field underscores the level of complexity the cancer research area has reached and requires the need for well-structured networks to provide expert platforms, rapid exchange of information to train future researchers in this new concept.

Description of EuroCSCT network

The virtual training platform established by the EuroCSCTraining Network gathered European excellency in cancer stem cell research comprising both laboratories from the academic and private sector as well as industrial partners, small entreprises and European associations dedicated in research, education and dissemination.

9 affiliated research laboratories:
Université Paris Diderot (FR), University of Oxford (UK), Medizinische Universitaet Wien (AT), Fondazione Centro San Raffaele (IT), Institut Curie (FR), Academisch Ziekenhuis Groningen (NL), University College London (UK), XenTech SAS (FR), Miltenyi Biotec GMBH (DE)

7 associated partners:
Cancer Research Institute (UK), Becton Dickinson (EU/FR), Stemcell (EU/FR), German Cancer Research Center in the Helmholtz Association (DE), European School of Hematology (ESH),
European Hematology Association (NL), Carrière et Capital Humain Consulting (FR).

The partners were selected on the need to provide complementary expertise for the common research program and overall training (cancer cell competence and career development) and their common aim to provide excellent training. The expected synergies were fulfilled thanks to the interdisciplinary and intersector expertise of the participants, such as: expert knowledge of cancer cell research, expert facilities and platforms, unique models and techniques, experience in PhD and post-doctoral training, open and collaborative qualities leading to cancer cell research accessibility to all young and more senior researchers.

The ESRs and ERs positions were offered worldwide and allowed to select out of more than a 1,000 applicants, 10 ESRs and 3 ERs of 10 different nationalities. 6 ESR of the 10 ESR recruited in EuroCSCTraining were female as well as 1 ER of 3. 53,8% of EuroCSCTraining fellows were female.

Major objectives achieved over the four years of the project

EuroCSCT achieved its training goals for the young researchers while reaching significant results in Cancer Stem Cell research together with the young researchers. These can be highlighted in four significant results:
1. The individual specific research project of the young researchers
2. The joint research program of the EuroCSCT consortium with the young researchers
3. The comprehensive training of the young researchers in the field of cancer stem cell research and for their career development
4. The exploitation and dissemination of the EuroCSCT training and results

1. The individual specific research project of the young researchers
A specific scientific project in cancer stem cell research was given to each young researcher (ERs and ESRs) for a one/two (ERs) or three year period (ESRs). All young researchers achieved significant results which allowed all of them to present their results at the final EuroCSCT meeting and even for some of them at international-level meetings as posters (9 in total) and as oral presentations (8 in total) .

Titles of the individual research projects of the ERs and ESRs:
ESR1: Mechanims Affecting the Efficacy of Epigenetic Therapies in AML
ESR2: Targetting Leukemic Stem Cells by DNA based inmmunotherapy in AML
ESR3: Identification of New Stem Cells Targets in Advanced Systemic Mastocytosis (ASM) and Mast Cell Leukemia (MCL)
ESR4: Establishing and Characterisation of Mouse Models of Myelodysplastic Syndromes
ESR5: The Multipotent Cell of Origin of B Cell/Myeloid Biphonetypic Leukemia
ESR6: Dissecting Interplay between Notch and p53 in Invasive Colorectal Cancer
ESR7: Targetting Genes in Brain Cancer Stem Cells
ESR8: Establishing human niche for MML-AF9 leukemia
ESR9: Role of miR-125 in the regulation of hematopoietic regulation
ESR10: The metabolic state to define leukemic stem cells
ER1: Evidence of changes in the marks of proteins of the PRC1 complex in Glioblastoma stem cells
ER2: Role of Cancer Stem Cells in Breast Cancer Resistance to Chemotherapy
ER3: Isolation and Molecular Characterization of Solid Tumor Cancer Stem Cells

The results which are already published are available from the EuroCSCT website. 2 patent applications resulted from the work of one ESR and two ERs.

2. The joint research program of the EuroCSCT consortium with the young researchers
Both the researchers and the young researchers of EuroCSCT joined their efforts in the establishment of technical guidelines for three major pending questions in the field of cancer stem cell research:

a) Choice of animal models for the study of the CSCs (WP2): Novel animal models were established or improved to better mimic the human cancer for example of brain cancers (ex glioblastomas), resistant breast cancers or hematopoietic malignancies (MDS). Novel tools to monitor and assess cancer cells or cancer stem cells with a reduced number of animals were used or the technology taught in the secondments. In vitro culture systems to replace animal models were evaluated and used as an alternative and/or complementary experiments. As the study of cancer stem cells relies on the use of animal models, the strongest impact was the training of the ESRs and ERs to animal research, acquiring certificates and know-how and complying with the 3”R” rule

b) Cell purification, cell culture, banking (WP3): the ESRs and ERs were trained in the identification of reliable methods of cell sorting and cell culture in order to:
a) Highly enrich tumor samples of cancer stem cells or cancer initiating cells
b) Facilitate in vivo engraftment
c) Provide cell populations validated by in vivo models as containing defined number of cancer stem cells to allow both large analysis (arrays in epigenetics, genetics, proteomics) and standardized pre-clinical trials of cancer stem cell targeting.
The participation of the three most implicated industries in the field of cancer stem cell research in this WP, such as that of Miltenyi® as a beneficiary, strengthened the technological and managerial expertise and training in this field. This WP was closely related to WP2 and WP4. Novels aspects of cell purification and/or separation were validated. A patent application of a new cell line and its derivatives to study a rare disease, mastocytosis (UMW) was achieved (Patent: WO/2013/064639).

c) Monitoring of cancer cells resulting from cancer stem cells (WP4).
Monitoring cancer cells is crucial for the assessment of disease initiation. Through the training of the EuroCSCT’s ESRs and ERs, the consortium achieved the validation of techniques performed in different models to monitor the phenotypic and genotypic biomarkers of cancer initiation. Several techniques and biomarkers used to monitor cancer stem cells in different models and systems were used, adapted or established, such as: - Cells of myelodysplasia in transgenic mice models; - Cells of glioblastomas in neurospheres; - Cells in glioblastomas in animal, - Cells of rare hematological diseases such as mastocytosis in immunodeficient mice; - Cells of resistant breast cancers BRGS mice; - Cells from tumors obtained in xenografts. These results summarized by the ERs and ESRs are published on the website. One major success was the identification a novel biomarker of cancer cell with a patent application in process with two beneficiaries and two ERs.

3. The training of the young researcher in the field of cancer stem cell research and in their own career development (WP1 and WP5)
Along with the training in their own research laboratories, all ESRs and ERs performed at least one secondment in another beneficiary’s laboratory either for the need of expert technical platforms or know-how required for their own projects or to reach a more comprehensive knowledge on cancer stem cell research. The self-evaluation of the training needs was also assessed on the cancer stem cell research competence booklet designed by the consortium (available on the website) and through the discussions with the supervisor and tutor. All partners have acknowledged the benefit of sharing supervision on complementary training issues with a tutor (scientific versus PCD) and the annual monitoring input by the supervisory board. Along with the seminars at the host institutions, the young researchers were asked to participate at 2 summer schools one of which involved two other ITN projects in similar fields (stem cells and aging) and at 4 international Workshops co-organized with associate partners, ESH and EHA.

To reach the objectives of their Personal Career Development training (awareness of an established network of research colleagues, adaptation of their CV with novel skills, oral and written presentation of results and discussions on working condition issues) and to be thus in the best position for their future careers, all ESRs and ERs benefited from 4 dedicated sessions organized by partner CCH, a one day session organized by partner Becton Dickinson from the private sector, at their own site, and several sessions during the two Summerschools. Two sessions dedicated to working conditions, in particular the aspects on Women in Science, were held at the Hydra Summerschool and during the PCD training sessions at UCL.
A regular self-assessment by the ESRs and the ERs themselves to raise their awareness to the questions they should ask themselves to identify their acquired skills and their pending needs was done using the Career Development Questionnaire established by the consortium with partner CCH (the PCD questionnaire is available on the website). Regular discussions with their tutors equally developed their awareness on this subject.

At the EuroCSCT final meeting, the young researchers presented orally in a two day session:
a) the results obtained on their own research projects,
b) the techniques they had used or set up and wished to transfer to others and
c) what skills they had acquired during their three years and what perspectives they were now considering for the future. 8 ESRs have still one further year of PhD pending, two have just finished their PhD and all the ERs had found future positions in less than 6 months.
The published results of their work along with their chosen technique(s) were published on the EuroCSCT website. The overall results of the consortium is of 215 (200PIs + 15-Fellows) publications which are inserted in the EuroCSCT website and the identification of novel biomarkers of chemotherapeutic drug response by two beneficiaries (MT and XT) and one novel cell line to study a rare disease (MUW) (Patent: WO/2013/064639).

4. The exploitation and dissemination of the EuroCSCT training and results (WP 6)

Patents: Two patents were acquired through the EuroCSCT network: one novel marker of cancer/cancer stem cell was discovered through the collaboration of two beneficiaries and their respective ERs during their work in the laboratory and their secondments and one cell line of mastocytosis (Patent: WO/2013/064639). The exploitation of the results and the filing of the patents were performed according to the Consortium Agreement successfully drawn with all beneficiaries.

Dissemination of the results of the EuroCSCT network through the EuroCSCT website :
A dedicated .eu project website with 33 pages in total: www.eurocsctraining.eu

Dissemination through organization of international meetings: To enhance the exchange of knowledge in the field not only for the benefit of the ESRs and ERs of the EuroCSCT network but also for all researchers in the field, the network organized with associate partners, ESH and EHA: 5 international meetings all held in Europe: France, Italy, Sweden, Netherlands (two of 3 days with over a 100 attendees, and three of one day with around 50 attendees).

Conclusion

The main originality of this project was the active participation in the research projects, supervision and training of the key industrial actors of the field. This has allowed fruitful and trustful collaborations between sectors, as well as adapted training for future needs in the private sector and strong exploitation of the results. The contact with the private sector partners directly through training sessions, visits and research projects or secondments helped to break the barrier between public and private sector careers and facilitate dialogue and communication, creating thus a better knowledge and recognition of competences for future long-term inter-sector collaborations. They were instrumental in the exploitation of results (patents) and strict transfer of good laboratory practice, compliance to regulations.

The originality of the consortium lies also in a common translation research in various cancers in a same project (solid tumors such as breast, colon, and brain to leukemias, acute cancer to more chronic proliferative preneoplastic disorders). This cross-tissue cancer-training program offered a more comprehensive approach to cancer research and future careers at a time where common pathways may be targeted in different tumors, opening possibilities in the field of personalised medecine .

Cancer remains one of the key major public health issues. Every year more than 3 million Europeans are diagnosed with cancer. The novel pathways and targets recently identified through the cancer stem cell concept and the whole genome sequencing have opened new research areas and enhanced research and innovation such as new supra-disciplinary tools, biomarkers, bio-engineering and anti-cancer drugs which the ESRs and ERs and the participants of this network have contributed to. It is expected that these newly trained young researchers will benefit European academic laboratories, hospitals, and European enterprises that will require adapted-human resources with skilled people to address these novel concepts and technologies.

All the partners of the EuroCSCT network as well as the ESRs and ERs wished that the training of young researchers in this complex and moving field should be pursued and that a network of all young researchers be created.

Contact

Jean-Baptiste Milon, (Project Manager)
Tel.: +33 1 57 27 90 12
Fax: +33 1 57 27 90 11
E-mail
Record Number: 193482 / Last updated on: 2017-01-12
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