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Scientist honored for work with paclitaxel

2011; Wiley; Volume: 117; Issue: 13 Linguagem: Inglês

10.1002/cncr.26285

1097-0142

Carrie Printz,

Microtubule and mitosis dynamics

When the National Cancer Institute (NCI) asked Susan Band Horwitz, PhD, to research paclitaxel (Taxol) in 1977, she eagerly agreed because she was intrigued by its unique chemical structure. She set about researching the molecule, never anticipating that paclitaxel would someday be used to treat millions of patients worldwide with cancers of the ovary, breast, and lung. For her efforts with paclitaxel and her commitment to cancer research, Dr. Horwitz received the Eighth Annual Lifetime Achievement Award from the American Association for Cancer Research (AACR) at their annual meeting in Orlando, Florida, on April 3, 2011. “There are many fine scientists who do excellent work, and unfortunately the drugs they're working on don't make it,” she says. “I feel very lucky, and I also feel that this award is a recognition of all those who work in this area of drug development. You really can't foresee that a drug is going to work until it is used in humans.” At the same time, she adds, her award recognizes the many researchers who have worked in her laboratory over the years. Dr. Horwitz is the Rose C. Falkenstein Professor of Cancer Research and cochair of molecular pharmacology at the Albert Einstein College of Medicine of Yeshiva University in the Bronx, New York. She also is associate director of experimental therapeutics at the Albert Einstein Cancer Center Through out her career, she has received many honors, including the American Cancer Society's 2008 Medal of Honor for Distinguished Service in Clinical Research. In addition, she is a member of the American Academy of Arts and Sciences, the National Academy of Sciences, and the Institute of Medicine. She served as president of the AACR from 2002 to 2003, is a fellow of the National Foundation for Cancer Research, and served on the external advisory group that evaluated and recommended sweeping changes in the NCI's drug screening and development systems. “Her remarkable career and pivotal scientific contributions have influenced our understanding of how cancer drugs work and how to translate that knowledge into improved strategic treatments,” AACR Chief Executive Officer Margaret Foti, PhD, MD, noted in an AACR news release. Dr. Horwitz began researching paclitaxel after 2 medical chemists isolated the molecule from the bark of the Pacific yew tree. She and her then graduate student Peter Schiff found that. paclitaxel causes cells to produce extra microtubules, which are filament-like structures that play an important role in cell division. The drug freezes these microtubules into bundles, rendering them unable to disassemble. As a result, the cancer cells can no longer divide, and they eventually die. Her work led to clinical trials and finally, in 1992, to approval from the US Food and Drug Administration of paclitaxel for the treatment of patients with ovarian cancer. The compound also has been helpful with other diseases. For example, it is used to coat stents for people with cardiovascular disease to keep tissue from growing back. It has also shown promise in the treatment of nerve degenerative problems. Recently, scientists found that paclitaxel helped injured spines to regrow in rats. Dr. Horwitz continues to research natural products as potential new drugs. “When you think of organisms I work with, like trees, bacteria, and sponges from the ocean, they all have something in common,” she says. “They've developed these chemical protections, and they've had many centuries to evolve and to develop these molecules that are quite specific. That's what makes these plants so interesting.” The original idea for the molecular structure of paclitaxel comes from the tree;no chemist would ever sit down and design it, she adds. “There's not a lot you can do to Taxol so far to make it better because it probably has evolved to be the best fit.” Dr Ilorwitz and her colleagues arc now studying the molecular mechanism that enables tumor cells to resist paclitaxel. She is hoping to identify epigenetic changes that could be reversed and provide another target for overcoming resistance. She notes that the more she and others study drug resistance, the more they see what a complex field it is. One major change may lead to multiple additional changes that cause resistance. “We're interested in combinations of Taxol and other drugs that can overcome resistance in tissue culture and in mice to see if we can develop some interactions,” she says. Dr Horwitz fell into her career somewhat accidentally. After graduating with her postdoctoral degree in biochemistry from Brandeis University in Waltham, Massachusetts, and then becoming pregnant with twins, she knew it would be difficult to work full time. Her advisor put her in touch with the head of pharmacology at Tufts University School of Medicine in Boston, Massachusetts, where she was able to work 3 days a week. “I had to learn pharmacology, and I loved it,” she says. “I loved the idea that a small molecule can do great things—you take an aspirin and your headache goes away.” What now concerns Dr Horwitz most is the lack of federal funding for research. “The real tragedy is the young people,” she says. “We will lose a generation of scientists. How can they come into this business if they can't get jobs or funds to support their labs?” I had to learn pharmacology, and I loved it. I loved the idea that a small molecule can do great things—you take an aspirin and your headache goes away.— Susan Band Horwitz, PhD She doubts she would ever receive funding today to research a molecule from a tree. “When I started to work with it, there was 1 paper in the literature: the original isolation and structure determination by [paclitaxel codiscoverer] Monroe Wall, PhD, of the Research Triangle Institute,” she says. “Today I don't think it would have gone anywhere.” Dr Horwitz says she and others like her are doing what they can to survive and pull through in this difficult funding scenario but that, ”It's a darn shame.” “It's a time when we're making a lot of progress in cancer, and we could make tremendous strides in making drugs that are much more specific for specific tumors, but we need the money to do it,” she says.