With an MD, not a PhD, how did you become a researcher?

I went to medical school in Paraguay, and although the research environment there wasn't as strong as I later found it to be in the United States, I was eager for experience. I took it upon myself to participate in research through, for example, courses taught by researchers abroad, and I worked on yeast as a medical student. My most important decision was to persist with my intentions to focus on research into disease therapies. I did that by surrounding myself with brilliant people who guided me to ask important questions. I think that research is more than techniques or methodology; it is about learning to ask those questions. As a physician, I know where the potential therapeutic targets are. Not having a PhD doesn't stop you doing research, but there is a credibility gap to be bridged between the medical and research fields.

How did you decide where to focus your research?

When I came to Baylor 12 years ago, I had the opportunity and time to think about how to establish a new research career. At the same time, my career expanded. Discussions with colleagues made me think about research avenues, and after spending two weeks reading everything about prostate cancer, I knew that I wanted to focus on the connections between nerves and cancer cells. I thought that the interactions were clinically significant yet had been ignored at the biological level. The first thing my team and I did was to create a prostate cancer model to explore any relationship between cancer and nerves. We found that prostate cancer cells interact with nerves and prompt tumours to grow along the nerve branches of the prostate gland. Nerve density in the prostate is highest in areas with cancer. Our model suggests that the growth of new nerves promotes the progression of prostate tumours.

How did you get the idea to explore Botox as a cancer treatment?

Understanding that nerves are functionally important to cancer opened up a category of neurotoxins that could act as cancer-fighting agents. Using animal studies, we've shown that Botox has the same effect as removing nerves from the prostate, which led us to propose it as a non-surgical way to fight tumours. This clinical trial will test whether Botox can activate antitumour activity.

What are the biggest challenges facing physician-researchers?

There is little understanding of the difficulties we face. People claim that physician-researchers are important, but it doesn't always translate into support. When you don't fit the criteria of a scientist or a physician and try to bridge the groups, it can be difficult for grant and paper reviewers to judge your expertise. How do you deal with that? You are persistent. Persistence is not being stubborn; it means creating networks and interacting with people at different levels.

How have you persisted?

One of the best things I did was to join the US National Cancer Institute Tumor Microenvironment Network. That was important because it exposed my research to a lot of new people. I also joined the US National Institutes of Health Specialized Program of Research Excellence for prostate cancer. It can be easier to get funding as part of a larger group than by applying as a sole investigator.

What does this creativity award mean to you?

I think science has to be creative and explore new ideas. Researchers tend to focus on mechanisms and forget that biology is many layers of genes, gene modification, protein interactions and organ function. It is possible to target biological phenomena with simple ideas. The trial funded by the award is simple, but could have a big impact. Simple, however, doesn't mean easy. The award is a stamp of approval from a big organization of basic scientists and clinicians that shows a willingness to develop a new target and a new way of treating cancer.

Where do you plan to take your career from here?

I think that science is going to change, because we're learning the limitations of reductionist science. Disease is complex and we need new tools to understand it. Clinical trials will have multiple markers per subject to monitor responses — at the gene, RNA and protein levels, and even outside the cell — to understand how a drug works. I am part of a wave tackling that complexity head-on.