Two recipients of the EAU RF seeding grant set to start new projects

03 May 2018 By Loek Keizer

Earlier this year, the EAU’s Research Foundation (EAU RF) announced the availability of two new grants for short-term studies, so-called ‘seeding grants’. A final selection from the 21 submissions was made during the Annual EAU Congress in Copenhagen, last March, following personal interviews with three of the candidates. The EAU RF is pleased to introduce the two recipients who will be granted €25,000 each for a one-year research project, the results to be presented at EAU19 in Barcelona.

Dr. Maarten Albersen (Leuven, BE) will be developing and validating a patient-derived xenograft NMRI nude mouse model for the in-vivo study of penile squamous cell carcinoma. The second recipient is Dr. Johannes Linxweiler (Homburg, DE). His research will concern tumour-metastasis crosstalk in prostate cancer, and examining the effects of primary tumour removal and the role of exosomes in an orthotopic xenograft model.

“We were impressed by the great nu number of good applications,” EAU RF Chairman Prof. Bjartell (Malmö, SE) said, looking back on the application process. “In this case we were delighted to support two projects that displayed an advanced methodology and a clear translation approach and aiming at clinical implementation.”

Penile Cancer

Dr. Albersen heard about the new grant from one of the residents at the University Hospital in Leuven, and then found out more online. “I applied to this grant because I thought a project that I had been contemplating for a while fitted this call perfectly,” Albersen explains. “The seeding grant is designed for young but independent researchers with a proven track record who want to start a new project and need starter’s funding in order to obtain larger funding later on when preliminary data is available. Hence, I believed that I had a quite good chance of making it to the last round of the selection process.”

Asif Muneer, UCLH London, co-applicant and educational lead on rare urogenital cancers in eUROGEN (left), and Maarten Albersen, Uinersity Hospitals Leuven, applicant and clinical lead on rare urogenital cancers in eUROGEN (right).

The final interview process was a good experience for Albertsen, discussing details of the project with Prof. Bjartell and Scientific and Clinical Research Director Dr. Wim Witjes (Arnhem, NL). “They were sincerely interested in the project and we had a pleasant conversation in a friendly atmosphere in which we discussed project details, particularly pertaining to feasibility and valorization issues, that had not been described in the rather short online application.”

“Penile cancer is an aggressive disease in which we to date have failed to provide very effective and personalized systemic and targeted treatments.”

Penile cancer is a relatively rare condition, and as a result, there are still large gaps in the understanding of the disease: “Basic and translational research on penile cancer are lagging behind compared to the ‘big’ urological cancers: prostate, kidney, bladder. Nonetheless, penile cancer is an aggressive disease in which we to date have failed to provide very effective and personalized systemic and targeted treatments. The envisioned research helps to fill this gap. As it is difficult to recruit patients with rare diseases for clinical trials, xenograft models may be used for preclinical in-vivo trials to select drugs that should be further tested in the human setting.”

Albersen’s project aims to establish reliable, validated and genomically stable xenograft avatar-mice mimicking metastasized penile cancer. “In a continuation of the project -and we hope that the results of the EAU-RF seeding grant will enable us to apply for larger funds to continue this line of research- we will be able to preselect drugs that are effective in penile cancer with a certain genomic fingerprint and mutational burden that will be promising for application in clinical practice. The model will further provide us with a detailed understanding on mechanisms of drug response and –resistance in penile cancer.”

Dr. Albersen’s research project will be developing and validating a patient-derived xenograft NMRI nude mouse model for the in-vivo study of penile squamous cell carcinoma.

“In further applications on the long term, we will use these models to test new systemic drugs that may be used in the setting of advanced or metastasized penile carcinoma, and study the biology of this rare tumour including mechanisms of resistance in order to explain and in the future overcome classically poor response rates to systemic therapy in penile cancer patients.”

Albersen and his team will collaborate intensively with Trace, a patient-derived tumour xenograft platform at the University of Leuven, who will provide them with the expertise of setting up and validating the xenograft models. “We aim to start with tumours of both HPV positive and -negative tumours of different squamous cell carcinoma subtypes. Ethical approval amendments and applications have been submitted, and as soon as they are approved, we are ready to start.”

“UZ Leuven is currently a high-volume penile cancer centre within eUROGEN, and we aim to have sufficient patients recruited and consented to start the first engraftment procedures end of summer-beginning of fall. We aim to have the first preliminary results by the Annual EAU Congress next year, and if not, we aim to have the full project completed by EAU20.”

Primary tumour removal

Dr. Linxweiler

Dr. Linxweiler was familiar with the activities of the EAU Research Foundation and found out about the seeding grant through the monthly EAU e-mail newsletter. Linxweiler: “I was excited to read that the EAU-RF was for the first time announcing seeding grants for highly-innovative projects, also including basic and translational research.”

His impression of the selection process was “very competitive but fair. When preparing my application I was actually not very confident in being selected as one of the two grantees, considering both the broad spectrum of high level research activities within the EAU community and the fact that -though scientifically active since the beginning of my residency four years ago- I am standing rather at the beginning of my academic career.”

“I was delighted to be invited as one of the final contestants. The interview itself in Copenhagen was very demanding but also a unique experience as I had the opportunity to discuss the strengths and weaknesses of my planned project including scientific, financial, infrastructural and personal aspects for almost an hour with three highly-renowned urologic scientists: Profs. Bjartell and Sharokh Shariat (Vienna, AT), and Dr. Witjes.”

The concept of primary tumour removal in oligometastatic prostate cancer has been a matter of intense debates over the past few years, with evidence (primarily from retrospective studies) suggesting a beneficial effect of cytoreductive prostatectomy. Prospective trials examining the benefit of cytoreductive prostatectomy are currently underway, however it might be difficult to recruit patients for such trials and it will take several years until reliable results will become available.

“We will examine the effect of primary tumour removal in metastatic prostate cancer in a highly standardized, sophisticated in-vivo model.”

“In our project, we will examine the effect of primary tumour removal in metastatic prostate cancer in a highly standardized, sophisticated in-vivo model,” Linxweiler explains. “We are aiming to gain insights into the biological mechanisms underlying the crosstalk between primary tumour and metastases, which are still largely unknown.”

Primary and goals and next steps
The primary goals of the experiments planned within this one-year project are to show that i) the removal of the primary tumour in an orthotopic prostate cancer xenograft model has an impact on further disease progression and metastatic spread (slowing it down) and that ii) it is methodologically possible to isolate extracellular vesicles (EVs) from mouse serum and tissue samples from primary tumours and metastases. Linxweiler: “The verification of our basic working hypotheses and the establishment of  experimental techniques will then pave the way for a larger project (two to three years) focusing on the EV-mediated mutual exchange of biomolecules between primary tumours and metastases in prostate cancer and its role for disease progression and therapy resistance.”

Transmission electron microscopy image of exosomes (scale bar = 100nm) from Dr. Linxweiler’s project.

On the envisioned effect that the research will have: “First, our project will provide high-level preclinical evidence for or against the use of cytoreductive radical prostatectomy in oligometastatic prostate cancer. Second, it will help to unravel the molecular mechanisms of primary tumour-metastasis interaction, thereby not only contributing to a better understanding of this emerging and paramount aspect of cancer biology but also providing new approaches for biomarker discovery and therapeutic intervention.”

Dr. Linxweiler will now start to organise all administrative matters that go together with the start of a new, externally-funded project, also setting up a multidisciplinary project team and planning and discussing the experiments in detail. “I will be the project leader and will be able to perform most experiments on my own as I have the opportunity to get regular time (usually one day a week) free from clinical duties to fully dedicate myself to scientific activities.”

“I will be supported by the head of urological research at our department (Prof. Kerstin Junker) and her laboratory team, the clinical director (Prof. Michael Stöckle) and members from the prostate cancer team (Dr. Matthias Saar, Dr. Türkan Hajili) at our department as well as members of the departments of clinical-experimental surgery, experimental radiology and medical biochemistry, so the project team will comprise about 5 to 10 people.”

EAU RF Chairman Prof. Bjartell is confident of the future potential of the seeding grant programme: “There is certainly a need for supporting similar projects in the future. The EAU RF will play an important role in promoting high-quality research of various kinds.”

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