Robert A. Weinberg and Angela M. Hartley Brodie awarded 2006 Landon-AACR Prizes for Cancer Research

PHILADELPHIA Two researchers whose pivotal discoveries have advanced progress against cancer by revealing vital information about the nature, origins and treatment of the disease are being honored with the 2006 Landon-AACR Prizes for Basic and Translational Cancer Research.

These prizes, offered by the Kirk A. and Dorothy P. Landon Foundation and the American Association for Cancer Research, are the largest awarded to cancer researchers by a professional society of their peers. Each winner will receive an unrestricted cash award of $200,000, and will present successive scientific lectures at the AACR Annual Meeting, in Washington, D.C., beginning at 4:30 p.m. on Monday, April 3, 2006, in Hall D of the Washington Convention Center.

This year's Landon Prize recipients are:

Robert A. Weinberg, Ph.D., a founding member of the Whitehead Institute for Biomedical Research, and professor of biology at Massachusetts Institute of Technology, both in Cambridge, Mass., who will receive the 5th Kirk A. Landon-AACR Prize for Basic Cancer Research; and

Angela M. Hartley Brodie, Ph.D., professor of pharmacology and experimental therapeutics at the University of Maryland School of Medicine in Baltimore and University of Maryland Marlene and Stewart Greenebaum Cancer Center researcher, who will be awarded the 5th Dorothy P. Landon-AACR Prize for Translational Cancer Research.

"These extraordinary scientists have spent their careers working to unravel at the molecular level some of cancer's most elusive mysteries," said Margaret Foti, Ph.D., M.D. (h.c.), Chief Executive Officer of the AACR.

"Each has spent more than 30 years in the laboratory, pursuing with relentless dedication their theories about cancer's mechanisms of invasion and progression in the complex chemistry of the human body," Dr. Foti added. "Their insights, creativity and determination have saved lives and paved new pathways of investigation for other cancer scientists to pursue. They have also been exemplary teachers and mentors of the next generation of cancer researchers. We are proud to recognize their accomplishments with these major prizes."

Robert Weinberg's major contribution to the groundbreaking discovery of human oncogenes--genes that cause cancer when mutated--started with a simple question: How does cancer begin?

"If one looks at a human tumor, one realizes it's a conglomerate of many cells which are growing, multiplying out of control," Dr. Weinberg told the "NewsHour with Jim Lehrer" on July 28, 1999. On that day, the British journal Nature published the report by Dr. Weinberg and his research team of their successfully converting normal human cells into tumor cells in a culture dish.

"Looking inside the cells," he continued "we identified a number of damaged genes, called oncogenes or tumor suppressor genes. They're the regulators that orchestrate the proliferation of the cell. For many years, we've been trying to figure out how these damaged genes force a normal cell to become a tumor cell. The problem, however, is that if one looks at human tumor cells, as isolated from patients, these cells have an unknown number of damaged genes, and so we've been hard-pressed to enumerate all of the genetic damage that is required to convert a normal human cell into a cancer cell, into a tumor."

Dr. Weinberg and his colleagues built upon the previous discovery of telomeres, specialized structures that define the ends of chromosomes. Every time a cell divides, the DNA at each telomere gets shorter. The enzyme responsible for maintaining telomere length, called telomerase, occurs at low levels in normal human tissues. In tumor cells, telomerase is more prevalent and more active, giving cells a longer than normal life span, that is, more time to replicate and grow.

The genes coding for telomerase proved to be the essential ingredients in the molecular cocktail which must be altered within a cell before it is transformed from the normal state to cancer. Once the Weinberg team learned the identities of the genes critical to tumor formation, they were able to effect the transformation in vitro. The search for the formula required to transform normal human cells into cancer cells took more than 15 years.

The Weinberg Lab continues to study the molecular mechanisms that control the growth of human tumors and their ability to seed distant growths--metastases. This work has revealed ways in which normal stromal (connective tissue) cells recruited into a tumor aid the growth and survival of the cancer cells. In addition, by studying genes that are normally active early in embryonic development, Dr. Weinberg and his colleagues have discovered mechanisms by which cancer cells in a primary tumor acquire the ability to invade nearby tissues and to spread to distant sites in the body.

"Cancer research has been a consuming passion of my life for three decades, and so it comes as an extraordinary honor that I am recognized in this way by my peers who include, by all measures, the world leaders in this dynamic and ever-fascinating field of science," said Dr. Weinberg. "I am extremely flattered. Never in my wildest dreams could I have imagined that my work begun three decades ago would lead to recognition of this sort."

Angela M. Hartley Brodie is being honored for discovering and developing a new class of drugs called aromatase inhibitors, which help prevent the recurrence of breast cancer in postmenopausal women. The drug works by interfering with aromatase--the enzyme that catalyzes the key step in the biosynthesis of estrogens--thereby stopping the production of the hormone that fuels the growth of cancer cells. Other drugs for the treatment of breast cancer, such as tamoxifen, block estrogen from binding to the estrogen receptors in cancer cells. Many breast cancers are hormone-dependent, requiring estrogen to reproduce and grow.

Dr. Brodie's interest in the role of estrogens in breast cancer arose early in her career while she was working as a research assistant in the Department of Hormone Research at the Christie Hospital in Manchester, U.K. Some 15 years later, in 1973, while a staff scientist at the Worcester Foundation for Experimental Biology in Shrewsbury, Mass., Dr. Brodie and her husband reported a number of compounds that are selective inhibitors of aromatase. They hypothesized that aromatase inhibitors might be better alternatives than tamoxifen, a weak antiestrogen which produces a slight estrogenic effect. Consequently, tumors are not always suppressed by tamoxifen; moreover, the drug no longer works after five years and increases the risk of strokes and endometrial cancer.

It was in 1982 when Dr. Brodie collaborated with colleagues in her native England to treat breast cancer patients with the aromatase inhibitor that had proved to be most potent in her studies. The compound 4-hydroxyandrostenedione (4-OHA) was synthesized in Dr. Brodie's laboratory at the University of Maryland School of Medicine in Baltimore, and her collaborators at the Royal Marsden Hospital in London successfully arrested tumors in women whose breast cancer was resistant to tamoxifen and other standard treatments.

After further trials, 4-OHA was introduced on the market as formestane in 1994. It was the first new treatment for breast cancer in a decade. Today, three aromatase inhibitors are approved for use by women with estrogen receptor positive metastatic breast cancer.

"Bringing a new discovery from the laboratory into the clinic is a long, involved process," Dr. Brodie told a writer for the University of Maryland Marlene and Stewart Greenebaum Cancer Center Web site last year.

"In the beginning, the scientific community was convinced that this new approach wouldn't work, that antiestrogens like tamoxifen were the only way to go," added Dr. Brodie, who was awarded the 2005 Charles F. Kettering Prize in recognition of her work. "We tried to interest a number of drug companies in developing these new compounds, but new drug development is a risky business and they were not terribly interested. It wasn't until we began conducting clinical trials with my colleagues in London on our compound formestane, and showing positive results in patients, that we were able to interest the pharmaceutical companies in developing this class of agents."

These studies and current clinical trials show aromatase inhibitors to be more effective than tamoxifen in first-line therapy and, more recently, in preventing breast cancer recurrence in women who received a five-year course of tamoxifen. Dr. Brodie is applying similar approaches

to develop novel agents for treating prostate cancer. Inhibitors targeting the enzymes that synthesize the male hormone androgen and its receptors are in development.

"To be selected for the Landon-AACR Prize for Translational Cancer Research is a tremendous honor, and I am very grateful to receive this recognition of my work," Dr. Brodie said. "I am very happy indeed that our work turned out to be beneficial for breast cancer patients."

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Editors Note: Photographs of Robert A. Weinberg and Angela M. Hartley Brodie can be downloaded from the AACR website, www.aacr.org. A concurrent release is being issued by the University of Maryland School of Medicine.

Founded in 1907, the American Association for Cancer Research is a professional society of more than 24,000 laboratory, translational, and clinical scientists engaged in all areas of cancer research in the United States and in more than 60 other countries. AACR's mission is to accelerate the prevention and cure of cancer through research, education, communication, and advocacy. Its principal activities include the publication of five major peer-reviewed scientific journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. AACR's Annual Meetings attract nearly 16,000 participants who share new and significant discoveries in the cancer field. Specialty meetings, held throughout the year, focus on the latest developments in all areas of cancer research. The Landon-AACR Prizes for Basic and Translational Cancer Research were launched in the summer of 2002 to promote recognize and reward seminal contributions to our understanding of cancer through basic and translational cancer research. These distinguished scientific prizes bring heightened public attention to landmark achievements in the continuing effort to prevent and cure cancer through high-quality laboratory and translational cancer research.

The Kirk A. and Dorothy P. Landon Foundation was created through a bequest from Mrs. Landon, who willed that her estate be committed to medical research, especially cancer research and research into cancer-related diseases. R. Kirk Landon, son of Kirk A. Landon, serves as chairman of the Foundation's Board of Trustees. The Foundation accomplishes its mission through a variety of programs and initiatives, the first of which were the Landon-AACR prizes.


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