Periodic Reporting for period 2 - TransPot (Translational Research Network in Prostate Cancer)
Reporting period: 2019-01-01 to 2021-04-30
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 was to provide an 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. The key objectives of the project were: (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 purpose of the training network was to provide an 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. The key objectives of the project were: (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 developed a robust management structure to coordinate and manage administrative, research and training activities and the appointed governance bodies have remained active throughout the project.
Training of our young researchers was the primary focus of the network. During the project, TransPot delivered four bespoke training courses for Early Stage Researchers (ESR). The first training course (TC1), Molecular Mechanisms and Clinical Aspects of Prostate Cancer was hosted by Erasmus MC (EMC) and took place in Rotterdam in January 2018. The second training course (TC2), Systems Biology/medicine and ‘omics’ Technology, was hosted by Biomedical Research Foundation of the Academy of Athens (BRFAA) in Athens in October 2018. Training course 3 (TC3), Clinical Management and Precision Medicine Prostate Cancer was hosted by University of Glasgow (UoG) in March 2019 and training course 4 (TC4), Methodologies and Infrastructure for Translational Research in Prostate Cancer was held in Porto in October 2019. TC 4 was held in collaboration with the TRAIN ITN (Grant No. 721532), allowing collaboration with a fellow Prostate Cancer project and interaction with likeminded ESRs. TC2 and TC4 were linked with ESUR (European Association of Urology - Section of Urological Research) annual conferences where ESRs had the opportunity to attend international conferences and showcase their research via poster or invited podium presentations to conference delegates from European academic institutions.
In addition to training courses, ESRs have attended local training events provided by host institutions. Secondments and collaborations within the consortium were extremely important to enable ESRs to gain new skills and experience of different research environments including academia and industry.
The TransPot International Conference, one of the main scheduled outputs for the project, was planned to take place as a workshop to be held in conjunction with the European Association for Cancer Research (EACR) conference in May 2020. Unfortunately, due to the COVID-19 pandemic, the in-person event was cancelled. Instead, TransPot hosted a virtual event ‘Integrated prostate cancer research across the European Union: The TransPot Collaborative Symposium’, containing a mix of ESR talks and invited speaker presentations. Positive feedback was received from both the scientific community and from ESRs.
Despite restrictions due to the COVID-19 pandemic, TransPot has disseminated its results using a variety of tools. TransPot produced an introductory video (https://www.youtube.com/watch?v=2bv07p6Awg0&t=4s) which acts as a great dissemination tool to explain the importance of TransPot’s research to the general public. The consortium has also undertaken a wide variety of dissemination activities including conference participation, exhibitions, and communication campaigns. Additionally, an article was published in European Urology Today (EUT), which provided details of the project and its aims, as well as a summary of the results achieved. High impact papers resulting from TransPot work have already been published, including publication of novel findings, as well as reviews and technical papers.
In the project, we have benefitted from the use of highly novel pre-clinical models of hormone and chemotherapy resistant prostate cancer to gain new knowledge in how prostate cancers develop resistance to treatment such as hormone manipulation. We have also established additional models where human prostate cancer cells were grown in a 3D environment generating prostate cancer organoids, which are comparable to ‘miniature organs’. Importantly, the specific tumour characteristics of the individual patient were maintained in these organoids, making our experiments clinically relevant.
Experimental approaches within the consortium using our wide range of models has provided a comprehensive collection of data from both prostate cancer cells and tissue samples. Analysis of this data has led to a list of genes and proteins implicated in the transition to hormone resistance, and we have identified novel signalling molecules and/or metabolic genes that may represent new targets for therapy. Our research has highlighted a protein called SLFN5 (Schlafen Family Member 5) as playing an important role in the transition to hormone therapy resistance and we have also identified a panel of molecules in urine that indicate advanced or aggressive prostate cancer, which could potentially be used as diagnostic test. Additionally, we have studied 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.
Through our collaborative strategy, studies involving the extensive range of pre-clinical and clinical models available have increased our understanding of incurable prostate cancer, and provided potential new targets for therapy to overcome treatment resistance in prostate cancer.
Training of our young researchers was the primary focus of the network. During the project, TransPot delivered four bespoke training courses for Early Stage Researchers (ESR). The first training course (TC1), Molecular Mechanisms and Clinical Aspects of Prostate Cancer was hosted by Erasmus MC (EMC) and took place in Rotterdam in January 2018. The second training course (TC2), Systems Biology/medicine and ‘omics’ Technology, was hosted by Biomedical Research Foundation of the Academy of Athens (BRFAA) in Athens in October 2018. Training course 3 (TC3), Clinical Management and Precision Medicine Prostate Cancer was hosted by University of Glasgow (UoG) in March 2019 and training course 4 (TC4), Methodologies and Infrastructure for Translational Research in Prostate Cancer was held in Porto in October 2019. TC 4 was held in collaboration with the TRAIN ITN (Grant No. 721532), allowing collaboration with a fellow Prostate Cancer project and interaction with likeminded ESRs. TC2 and TC4 were linked with ESUR (European Association of Urology - Section of Urological Research) annual conferences where ESRs had the opportunity to attend international conferences and showcase their research via poster or invited podium presentations to conference delegates from European academic institutions.
In addition to training courses, ESRs have attended local training events provided by host institutions. Secondments and collaborations within the consortium were extremely important to enable ESRs to gain new skills and experience of different research environments including academia and industry.
The TransPot International Conference, one of the main scheduled outputs for the project, was planned to take place as a workshop to be held in conjunction with the European Association for Cancer Research (EACR) conference in May 2020. Unfortunately, due to the COVID-19 pandemic, the in-person event was cancelled. Instead, TransPot hosted a virtual event ‘Integrated prostate cancer research across the European Union: The TransPot Collaborative Symposium’, containing a mix of ESR talks and invited speaker presentations. Positive feedback was received from both the scientific community and from ESRs.
Despite restrictions due to the COVID-19 pandemic, TransPot has disseminated its results using a variety of tools. TransPot produced an introductory video (https://www.youtube.com/watch?v=2bv07p6Awg0&t=4s) which acts as a great dissemination tool to explain the importance of TransPot’s research to the general public. The consortium has also undertaken a wide variety of dissemination activities including conference participation, exhibitions, and communication campaigns. Additionally, an article was published in European Urology Today (EUT), which provided details of the project and its aims, as well as a summary of the results achieved. High impact papers resulting from TransPot work have already been published, including publication of novel findings, as well as reviews and technical papers.
In the project, we have benefitted from the use of highly novel pre-clinical models of hormone and chemotherapy resistant prostate cancer to gain new knowledge in how prostate cancers develop resistance to treatment such as hormone manipulation. We have also established additional models where human prostate cancer cells were grown in a 3D environment generating prostate cancer organoids, which are comparable to ‘miniature organs’. Importantly, the specific tumour characteristics of the individual patient were maintained in these organoids, making our experiments clinically relevant.
Experimental approaches within the consortium using our wide range of models has provided a comprehensive collection of data from both prostate cancer cells and tissue samples. Analysis of this data has led to a list of genes and proteins implicated in the transition to hormone resistance, and we have identified novel signalling molecules and/or metabolic genes that may represent new targets for therapy. Our research has highlighted a protein called SLFN5 (Schlafen Family Member 5) as playing an important role in the transition to hormone therapy resistance and we have also identified a panel of molecules in urine that indicate advanced or aggressive prostate cancer, which could potentially be used as diagnostic test. Additionally, we have studied 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.
Through our collaborative strategy, studies involving the extensive range of pre-clinical and clinical models available have increased our understanding of incurable prostate cancer, and provided potential new targets for therapy to overcome treatment resistance in prostate cancer.
We have identified SLFN5 protein to be a key player in castration resistant prostate cancer. If SLFN5 (and/or its downstream partners) is confirmed to be a valid target for treatment, there will be significant societal benefit from the development of new treatment of lethal prostate cancer. In other projects, our research partners have successfully identified biomarkers in tissue or urine samples of prostate cancer sufferers. Collectively, these findings will create new opportunities to develop better tests to detect lethal prostate cancer and thus improve management plan for patients in the future. Our outreach and dissemination efforts are designed to give added value to our research output, reaching out to the scientific and clinical communities, and to the lay public. Through a combination of engagements on social media and scientific communications (publications and conference presentations), we have fulfilled our plan in sharing our research activities and key findings with our target audience.