The EAU RF’s “start-up package” for beginning researchers

09 October 2020 By Loek Keizer

Dr. Alvaro Aytes (Barcelona, ES) was finishing his postdoc in the United States when he started exploring funding opportunities for a new research project. “I was an associate research scientist at Columbia University in New York, and after seven years I wasn’t that well connected to European funding opportunities anymore. I think it was through friends and colleagues that someone pointed out the EAU Research Foundation’s Career Development Programme.”

The programme was started by the EAU Research Foundation in 2012, in order to help researchers in urology start projects and prove their viability, thereby attracting new funding. The three-year programme helps promising researchers make a jump from a mentored position to leading their own projects and in turn employ others.

“The development programme has been instrumental in helping me develop my own ideas,” says Dr. Aytes. “The most important thing when you transition from a postdoc position to a non-mentor position is that you might have a contract with an institute, but that doesn’t mean you have funding to move your projects forward. This programme acted as a start-up package. Its funds allowed me to hire the first postdoc in my lab, the first technician, and basically start running a lab: ordering supplies and getting things started.”

Dr. Aytes is the principal investigator for this project, which falls under the Programme Against Cancer Therapeutic Resistance (ProCURE). It explores causal mechanisms and novel therapeutic targets in castration-resistant prostate cancer after the failure of androgen receptor blockers. It is a joint project between the Catalan Institute of Oncology (ICO) and the Bellvitge Institute for Biomedical Research (IDIBELL). The project recently finished its third year and yielded the first promising results, important new publications for the team and secured new streams of funding to continue the research.

Selection process
The selection process for the programme took place in 2015 and involved several rounds of interviews and presentations. Dr. Aytes found the process “very interesting. I would say it’s a fine example of how you would recruit people if you’re going to spend a substantial amount of money to launch their careers.”

After a round of reviews of the submitted projects, there is a second round that involves a face-to-face interview with the EAU Research Foundation’s committee with every candidate who makes it onto a shortlist. These interviews take place at the EAU’s Annual Congress, in the case of this project in Madrid in 2015.

“The face-to-face interview was not unusual but I found that the committee was a nice mix of clinicians and basic scientists who posed interesting questions and comments in a positive way. They weren’t out to tear the proposals apart and select the one that survives. I felt they were looking for interesting ideas that could help move forward the organisation’s strategic plan. It was a pleasant but also demanding process.”

The Project
Dr. Aytes’s research focuses on advanced prostate cancer and mechanisms of resistance to standard of care treatments. His team is trying to identify new targets or vulnerabilities that emerge from treatment on PCa patients, offering new opportunities for intervention. This includes new targets but also new biomarkers to better stratify patients based on risk or to predict whether treatment may work better or worse in a particular subset of patients.

“We do a lot of work with mouse models,” says Dr. Aytes. “We’re basic researchers with a translational point of view so we try to use experimental models, which includes cell-based models or animal models. We model the disease as it progresses from androgen receptor-responsive phases of the disease to castration-resistant PCa, or even androgen-independent PCa where there is a great need for better treatment and the ability to predict who’s going to respond to the treatment available.”

“That was the main goal of the career track programme: identify new targets and biomarkers in the realm of epigenetics. Epigenetic markers and targets that could predict or could be used as epigenetic targets.”

“The project emerged from earlier data during my postdoc. I conceived it and wrote about it during my postdoc period in New York. When the project was accepted, I took the know-how and some animal and cellular models that I had developed during the postdoc years in NYC back to my home institution in Barcelona.”

“I should point out that another important aspect of the career track is that it was very flexible with dates, with budget allocation. Typically in science, and especially when starting a project, this is an important factor. The organisations that are funding your work need to understand that you need a certain level of flexibility to allocate funds to either reagent, hiring personnel, or in this case shipping mice across the Atlantic. The EAU-RF understands that. That’s why I think that the career track programme is an excellent programme for essentially what it’s meant to be: launching careers in research.”

Response
One of the major conclusions following the three years of research is that collectively, the preliminary data strongly points at nuclear receptor binding SET Domain Protein 2 (NSD2) as a potential biomarker for lethal prostate cancer that is functionally linked to metastasis and whose inhibition with small molecules may provide a therapeutic opportunity in advanced prostate cancer.

The project has generated several publications (see references below), drumming up interest in the research, and ultimately more funding, most notably in Nature Communications in December 2018. Work is currently underway on an article for European Urology. “Being published in such a prestigious and widely-cited journal will be the icing on the cake for this project and for the Career Development Programme as a whole,” Dr. Aytes reflected.

“It can be difficult to get visibility sometimes, especially coming from a small institution, but I can’t complain. Papers published so far have been highly cited. As a result of these papers I’ve been invited to the French Association for Prostate Cancer, and to conferences and congresses throughout Europe. I was invited to participate in research consortiums for European funding. This is the result of the work that the career programme has allowed me to do.”

As the cooperation with the EAU Research Foundation winds down, the project has generated promising data that is attracting new interest.

“We’re a relatively young lab, but if this new paper gets accepted there will be a lot more to come. I’m very excited about this other follow-up work, on the role of epigenetics program in advanced disease. It will open up new strategies for stratifying patients. There is some know-how, intellectual property that can be derived that will come out from that paper. In terms of new targets for intervention, likely. Obviously there’s confidentialities there. But I think these next two papers in the pipeline are going to be great.”

Summarising the role of the Career Development Programme in the project’s success, Dr. Aytes points to the “start-up package” nature of the funding.

“Unquestionably, the programme’s funding gave me the ability to hire a postdoc right away, and a technician. It also gave me the possibility to immediately start generating results and attracting further funding.”

“Looking around me at other young investigators, it’s difficult to submit an application for funding by saying that you have a brilliant idea but you don’t have any funds yet. I’ve been able to say, “I have a brilliant idea, but this important association [the EAU] already trusts us.”

“We are now up and running, and that was thanks to the Career Development Programme.”

  • At the moment the EAU Research Foundation is focussed on supporting clinical research by young urology researchers through its Seeding Grant Programme. Find out more here

References
1. Aytes, A*., Giacobbe, A., Mitrofanova, A., Ruggero, K., Cyrta, J., Arriaga, J., Palomero, L., Farran-Matas, S., Rubin, M.A., Shen, M.M., et al. (2018). NSD2 is a conserved driver of metastatic prostate cancer progression. Nat Commun 9, 5201. https://www.nature.com/articles/s41467-018-07511-4

2. Costas, L., Frias-Gomez, J., Guardiola, M., Benavente, Y., Pineda, M., Pavon, M.A., Martinez, J.M., Climent, M., Barahona, M., Canet, J., Paytubi, S., Salinas, M., Palomero, L., Bianchi, I., Reventos, J., Capella, G., Diaz, M., Vidal, A., Piulats, J. M., Aytes, A., Ponce, J., Brunet, J., Bosch, F. X., Matias-Guiu, X., Alemany, L., de Sanjose, S. and Screenwide, Team (2019a). New perspectives on screening and early detection of endometrial cancer. Int J
Cancer 145, 3194-3206.

3. Costas, L., Palomero, L., Benavente, Y., Guardiola, M., Frias-Gomez, J., Pavon, M.A., Climent, M., Martinez, J.M., Barahona, M., Salinas, M., Pineda, M., Bianchi, I., Reventos, J., Capella, G., Diaz, M., Vidal, A., Piulats, J. M., Ponce, J., Brunet, J., Bosch, F. X., Matias-Guiu, X., Alemany, L. de Sanjose, S., Aytes, A*. and Screenwide Team. (2019b). Defining a mutational signature for endometrial cancer screening and early detection. Cancer Epidemiol 61, 129-132.

4. Nombela, P., Lozano, R., Aytes, A., Mateo, J., Olmos, D., and Castro, E. (2019). BRCA2 and Other DDR Genes in Prostate Cancer. Cancers (Basel) 11.

5. Piulats, J.M., Vidal, A., Garcia-Rodriguez, F.J., Munoz, C., Nadal, M., Moutinho, C., Martinez-Iniesta, M., Mora, J., Figueras, A., Guino, E., Padulles, L., Aytes, A., Mollevi, D. G., Puertas, S., Martinez-Fernandez, C., Castillo, W., Juliachs, M., Moreno, V., Munoz, P., Stefanovic, M., Pujana, M. A., Condom, E., Esteller, M., Germa, J. R., Capella, G.,Farre, L., Morales, A., Vinals, F., Garcia-Del-Muro, X., Ceron, J., Villanueva, A. (2018). Orthoxenografts of Testicular Germ Cell Tumors Demonstrate Genomic Changes Associated with Cisplatin Resistance and Identify PDMP as a Resensitizing Agent. Clin Cancer Res 24, 3755-3766.

6. Ruggero, K., Farran-Matas, S., Martinez-Tebar, A., and Aytes, A*. (2018). Epigenetic Regulation in Prostate Cancer Progression. Curr Mol Biol Rep 4, 101-115.

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