R ESE A RC H

Spotlight

Questions & answers:

Dr. Stephen Safe, Distinguished Professor Dr. Stephen Safe

by Sara Carney Dr. Stephen Safe is a distinguished professor in the Department of Veterinary Physiology & Pharmacology at the Texas A&M University College of Veterinary Medicine & Biomedical Sciences (CVM). In the past, Safe has researched the mechanisms of environmental toxins and their effects in humans and animals. Currently, Safe is focused on understanding and developing treatments for cancer that do not harm healthy cells. SC: What are you working on now? As I understand it, your research is involved in environmental toxicology and cancer. SS: I started doing toxicology research with dioxins, PCBs (polychlorinated biphenyls), and all sorts of related environmental toxicants and tried to understand their mechanism of action and toxicology. It turned out that these molecules act through a receptor—the Ah receptor­— and this can induce toxicity. In some cases, the responses can be protective. For example, the environmental toxicant TCDD (dioxin) causes liver toxicity in most species. However, TCDD also 28 •

• Summer 2014

inhibits the growth of breast cancer cells and tumors. We are developing “non-toxic” analogs of TCDD for cancer chemotherapy. We have three different ongoing projects, targeting three different factors in cancer cells and tumors. These factors are important for tumor growth and metastasis. We’re trying to develop drugs to target those three factors. Our focus has been on the design of new agents that will preferentially kill cancer cells but spare non-cancer tissue. SC: It sounds like your research has any number of One Health implications that would be relevant to the public. How do you communicate your research to the public? SS: My focus is on publishing our results in respected cancer journals and interacting with cancer patients individually. People understand that cancer is complicated, and what we’re trying to do is target genes or proteins in cancer cells that will kill the cancer cell but spare, as much as possible, normal cells. In addition, we have also been investigating the mechanisms of action of some widely used drugs—like aspirin and metformin—and have discovered common mechanisms among several different classes of anti-cancer agents. SC: Okay, so you’re interested in finding that common link? SS: If you don’t understand how a drug works, then it is difficult to design a clinical application. SC: Is this something that could be carried over into the veterinary world? SS: Oh, absolutely! We’ve done some work with Dr. Heather Wilson-Robles with the anti-inflammatory drug tolfenamic acid in canine cancer cells used in cultures, and we get very similar results to what we observe in human cancer cells. I think our work with tolfenamic acid could be used in veterinary medicine for cancer chemotherapy. SC: How has the research changed over time? Have you seen any trends in your career? SS: Everything is far more sophisticated, because we know the genome and what affects the genome and what genes are important. The tools we have now are outstanding. But when you think of it, the overall mortality rate from cancer is still high and only slowly improving; the new drugs on the market have made an impact, but a lot still needs to be done. Many of the drugs we use now are based on the same principles that were discovered almost 50 or 100 years ago— these include using highly toxic drugs that kill cancer cells but have lots of adverse side effects. This approach has been successful to some extent, but we need to develop drugs that specifically kill the cancer cell but spare the other cells. That’s essentially what we’re trying to do. SC: What are some of the challenges that you face in your research? SS: The challenges that I have now are the same the challenges that everybody else has—funding. I’ve always been well funded by the National Institutes of Health, but now it’s just desperate. Funding is really, really tight.