Cancer Researcher Wins Alpert Prize for Developing Taxol

Susan Horwitz has won the Alpert Prize for her early research on the biological action of paclitaxel (Taxol).

The Warren Alpert Foundation has announced that the winner of its 17th annual Alpert Prize is Susan Band Horwitz, the Falkenstein professor of cancer research and co-chair of the Department of Molecular Pharmacology at the Albert Einstein College of Medicine. The foundation recognizes Horwitz, a molecular pharmacologist, for her seminal contributions to understanding how the antitumor agent paclitaxel (Taxol) inhibits the growth of cancer cells. Her research laid the groundwork for studies leading to approval of the plant compound for the treatment of ovarian, breast, and lung cancers. The foundation will award Horwitz a $150,000 prize at a ceremony on Sept. 29, following a symposium at HMS titled “Challenges in the New Era of Cancer Therapeutics—Ongoing Lessons from the Development of Taxol.”

“One thing that Mr. Alpert stipulated when he developed this prize was that it should go to someone who had already made major contributions to helping patients. The impact of Susan’s work has been quite extraordinary in the cancer field,” said Dominick Purpura, dean of Albert Einstein College of Medicine, who nominated Horwitz for the prize.

In the United States, Taxol was first approved by the Food and Drug Administration for the treatment of refractory ovarian cancer in 1992. Approval for metastatic breast cancer followed in 1994, and more recently for non–small cell lung cancer in 1999. “Taxol has become one of the most valuable cytotoxic chemotherapeutic agents we have in clinical oncology. It has proven effective in ovarian, breast, lung, and head and neck cancer, and it has contributed immensely to the quality of life of cancer patients,” said Lawrence Shulman, HMS associate professor of medicine at the Dana–Farber Cancer Institute. The drug has been used in well over a million patients worldwide.

In 1977, Horwitz was approached by the National Cancer Institute to study the biological activity of paclitaxel. The compound had been isolated from the bark of the Pacific yew tree (Taxus brevifolia) in 1966 as part of an effort to find natural products that might cure cancer. At that time it was shown that paclitaxel was cytotoxic to cells growing in tissue culture, but over the next 10 years there was almost nothing further gleaned about its biological action. Within a few months of receiving her first samples, however, Horwitz and her then graduate student, Peter Schiff, found that paclitaxel inhibited cell division. In subsequent studies she showed that the compound interferes with mitosis by disrupting the normal function of microtubules.

“Susan’s discovery that Taxol bound to and stabilized microtubules, thereby blocking cells in mitosis meant, in fact, that Taxol was a prototype for a new class of chemotherapeutic drugs. Susan recognized this immediately, and it was also quickly sensed by the NCI and others, who then moved Taxol into clinical trials and then pervasive clinical use,” said Purpura.

Work from Horwitz’s laboratory revealed that paclitaxel binds specifically to beta-tubulin in the microtubule and causes microtubule bundle formation within the cell. But there are many different types of tubulin in the human body that are expressed in tissue-specific patterns. Today, Horwitz, who is a past-president of the American Association for Cancer Research, continues her work with paclitaxel, investigating whether the presence of different forms of tubulin might explain why some cancer cells are more responsive to the drug than others.

Chelsea, Mass., native Warren Alpert first established the Alpert prize in 1987, honoring Kenneth Murray of the University of Edinburgh, who had developed a successful vaccine for hepatitis B. To choose subsequent recipients, Alpert asked Daniel Tosteson, then dean of HMS, to convene a panel of experts to select and recognize renowned scientists from around the world whose research had a direct impact on the treatment of disease. Today recipients are selected by the foundation’s scientific advisory board, made up of internationally recognized biomedical scientists and chaired by Joseph Martin, dean of the Medical School.

—Tom Fagan

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