Eva Estébanez «If we can prevent androgen receptor dimerization, we can stop the progression of prostate cancer»

Dr. Eva Estébanez leads a research project that has detected a new family of compounds that paves the way for the development of new drugs to combat prostate cancer, the most common tumour in men. This group of researchers is in the process of creating a spin-off that will allow them to make the necessary steps to take their research to society.

What is the difference between conventional prostate cancer drugs and your inhibitors?

Most of the drugs that have been developed since the 1960s have consistently focused on the androgen receptor, specifically on the hormone binding site. What we propose is to design drugs at a different location that is far removed from where the hormone is. This is a new pharmacological area and therefore we will have to create totally different compounds without relying on current drugs for guidance. We use a very powerful and precise technique that allows us to visualize the androgen receptor, atom by atom, and this will in turn help us see what type of molecule we should design and in what specific place we should bind it. We have quite a few ideas and a very clear proof of concept that there is another place of the molecule in the protein where we can make drugs.

The protein we study works in a dimeric way, that is, there are two copies of the androgen receptor performing the same function. We hope to inhibit and disrupt this dimer and to stop the progression of cancer. Current drugs prevent the hormone from binding and the protein from going into the cell nucleus through a different mechanism. Unfortunately, it has been observed that a whole series of mutations in patients generate resistance over the years. Therefore, these drugs may be effective for one, two, or three years, but after that they are no longer beneficial. The protein begins to identify conventional inhibitors as if they were a hormone, and instead of inhibiting cancer cell growth they boost it. With our drugs we want to prevent the dimer from initiating gene transcription and the tumour from progressing towards metastasis.

How has the FBG Fund for the Promotion of Innovation (F2I) helped you?

First we got a Valorisation Fund (FVal) grant from the F2I and I think it was essential to orient our project. We had a series of hypotheses, and thanks to the FBG grant we were able to carry out the first experiments, which suggested that not only did we have a hypothesis, but that this hypothesis could become a reality. At the same time, we obtained a Mentor in Residence (MIR) grant, also within the framework of the F2I programme, which allowed us to hire a mentor with experience in the world of business creation and in turning a basic science project into the development of a drug that can reach society. The two grants have been key to directing and orienting the project and to prioritizing the activities needed to transform our idea into a reality. Our mentor was Jordi Naval, who has a proven experience in the creation of successful companies. At the beginning of the adventure, this helped us not only to get acquainted with the entrepreneurial ecosystem here in Catalonia, but also to have contact with both national and international investors and to learn concepts that are quite alien to scientists, such as the business plan, market research, the protection of our results, the regulatory framework, and so on.

We have also received a CaixaImpulse grant from laCaixa, thanks to which we now have another mentor, José Luis Cabero, who has extensive experience in international business. All of this has been a learning experience that I personally have found very encouraging and very motivating. It has opened up a world that enriches my work as a researcher and that we need in order to help our idea to reach prostate cancer patients.

Up until now scientists thought we knew everything, but we have realized that there is another world that we didn’t know about but that we need to take our idea to market.

What is the status of the project?

We are currently carrying out valorisation actions to improve these chemical molecules and to be able to conduct experiments in cells, followed by experiments in animal models. This is our goal for this year and the first half of next year. Thanks to the FVal (F2I) we were able to carry out the first valorisation actions, and now, thanks to the CaixaImpulse grant, we will take all the necessary actions to be able to conduct these experiments, which are key in the pre-clinical phase of drug development.

What drove you to create a spin-off?

I see the concept of the spin-off as a mechanism that will allow us to take the series of steps and actions necessary for our research to reach society. We are in the process of seeing how to do all this, but the idea is clear, we want to create a spin-off. At the moment we are analysing how to put all the pieces together with the collaboration of our mentors as well as with the other researchers who participate in the project: Dr. Pablo Fuentes, from the Research Institute of the Hospital de la Santa Creu i Sant Pau, and an American partner, Dr. Arnold T. Hagler, who has ample experience in the creation of biotech companies. We are also holding meetings with both national and international venture capitalists to obtain the funding we need. All the support that the FBG is giving us through Jose Conde and Inma Íñiguez with their experience in business creation is also indispensable and a key support.

We have a lot of experience working together with pharmaceutical companies, and we know that our project has aroused interest both nationally and internationally. Our idea is to perform tests leading up to animal models, check that our molecules can really become drugs, and then licence these molecules to a large pharmaceutical company so that they can reach the clinical trials phase. We have a number of recognized collaborators and we are analysing the best strategies to plan all actions in detail.

How important is knowledge transfer?

I believe it is fundamental for all the research we do to have an impact on society. There must be a return, and in our case, given that we work in a biomedical field, what we want is for all our research to be able to improve people’s lives. If we can procure drugs for a patient sector that currently does not have any, or drugs that have fewer side effects to improve the quality of life of patients, I believe that such transfer is essential and the objective that gives meaning to our research. Our conception of research on the one hand includes conducting basic research, because it is essential for the advancement of society, and on the other, transferring it to impact on the quality of life of patients.

More about Eva Estébanez

What’s the best advancement in history?

I may be biased by the fact that we use X-ray crystallography, but I believe that both the discovery of X-rays and their biomedical applications are among the greatest advancements we have had over the years.

The invention you are most afraid of?

At the moment I’m not afraid of any invention. Any invention can save lives and at the same time, in the wrong hands, do the opposite.

What would you like to see?

I would like that, even if there are some types of cancer that we do not manage to cure, these become a chronic disease perfectly compatible with a good quality of life. I am asthmatic since I was 4 years old, and I wish that these people could say “I have cancer”, but that this did not really imply that their life would be shortened.

The FBG is…

a fundamental tool for the University of Barcelona in order to dynamize all the research that its researchers carry out. I am very satisfied with the work done at the UB, which I believe is comparable to what other universities do in other countries where I have been, such as Germany and the United States. The FBG and the UB do an impeccable and excellent job both in the field of research and in the field of teaching. I believe that all the areas necessary to support researchers have been detected by the FBG and, despite not having the same budget as centres with greater funding, their work is comparable and in some cases I would dare to say that of a higher level of excellence. Since my return to Barcelona and the creation of my research group nine years ago, I can say that the FBG has been a fundamental part of the many scientific and transfer activities that I have developed at the University of Barcelona.

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