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Translational Research Network in Prostate Cancer

Periodic Reporting for period 1 - TransPot (Translational Research Network in Prostate Cancer)

Reporting period: 2017-01-01 to 2018-12-31

TransPot (The Translational Research Network for Prostate Cancer) is an innovative programme designed to tackle incurable prostate cancer (PC). Prostate cancer is a global health concern and is an important cause of premature cancer related deaths in men. Treatment resistance remains a challenge and patients with cancer relapse following previous hormone treatment tend not to respond well to treatment. Therefore there is an urgent need to find better treatment for patients who are resistant to current therapies. This will allow improved outcome among prostate cancer sufferers, hopefully with extended survival and better quality of life, and will have direct societal and economic impacts.

The purpose of the training network is to provide excellent opportunity for a group of young researchers to receive training in becoming translational scientists in the field of cancer biology, therapeutics development and biomarker discovery. Cutting edge technologies and invaluable laboratory and clinical resources are available to the network. The key objectives of the project are: (1) to gain better understanding of treatment resistant prostate cancer, (2) to find new treatment strategies to overcome treatment resistance, (3) to discover new tests or methods to predict cancer response to treatment and the likelihood of cancer progressing after treatment, (4) to develop a holistic tool for ‘tailor-made’ treatment for individual patients with treatment resistant prostate cancer.
The project has developed a robust management structure to coordinate and manage administrative, research and training activities of the consortium as a whole. To ensure dependencies across participants and minimise risk, Work Packages are managed effectively with the support of the Project Administrator and Scientific Programme Manager. A governance structure and relevant boards (General Assembly, Supervisory Board, Training sub-committee, Intellectual Property Rights and Dissemination sub-committee, Expert External Advisory Board) were established from the start of the project.

Training of our young researchers forms high priority in the network. The first two training courses were very well received with excellent feedback from both young researchers as well as the supervisors. The discussions on key scientific issues are highly relevant and timely. The first training course (TC1), Molecular Mechanisms and Clinical Aspects of Prostate Cancer ran over 3 full days and took place in Rotterdam between Wednesday 17th and Friday 19th January 2018. The second training course (TC2), Systems Biology/medicine and ‘omics’ Technology, was hosted by BRFAA in Athens between Tuesday 2nd and Thursday 4th October 2018. We have demonstrated initiative in linking our training course with an international meeting (European Association of Urology Section of Urological Research Annual Conference), which provided our students additional opportunity to present their work and to develop their ability in networking. We have also formed an alliance with another Innovative Training Network during the conference, and we are intending to host a joint training course in the coming year. We have been active in developing our outreach portfolio with a TransPot website, twitter account and Facebook page. Additionally, our researchers have participated in conferences, including giving oral and poster presentations, as well as publishing some of their work.

The secondment programme is progressing well with our students benefiting from the opportunity to carry our pertinent research for his/her project under the direct supervision of experts in the field, not available in their host laboratory.

In the project, we benefit from the use of highly novel pre-clinical models of hormone and chemotherapy resistant prostate cancer. We are interested in gaining new knowledge in how prostate cancers develop resistance to treatment such as hormone manipulation, and experimental approaches within the consortium using these models has provided a comprehensive collection of data from both cells and tissue samples which are now being interrogated. Analysis of this data has already led to a list of genes and proteins implicated in the transition to hormone resistance, and we have now identified novel signalling molecules and/or metabolic genes that may represent new targets for therapy. These new targets are being pursued within the network. We are also interested in probing the ‘environment’ in which the cancer grows, which represents critical interactions between the cancer and the host (patient). Increasingly these interactions are recognised to determine how cancer responds to treatments. We have set up highly novel and complex laboratory co-culture systems whereby cancer cells are grown in close proximity to other cells such as stromal cells (fibroblasts) or even immune cells. We have also developed a number of unique pre-clinical mouse models including genetically engineered mouse models and patients derived xenografts in mouse. Using these resources and other tools available, we have been studying how the androgen receptor (a key factor in prostate cancer development and progression) works in hormone resistant prostate cancer and what other molecules are involved. Collectively through these experiments, we hope to find new targets for therapy to overcome treatment resistance in prostate cancer.
By the end of the project, we are hopeful that candidate targets for therapy can be robustly confirmed. This will then provide a firm basis to launch a drug discovery campaign as a platform to develop new medicine. We will also develop new tests to go with the new treatment. If successful, we will improve the patient outcome with impact on health, economics and quality of life. The outreach and dissemination activities from this project will educate the public (including prostate cancer sufferers and their families), research community and clinical/health providers alike.