- © 2007 Canadian Medical Association or its licensors
Advances in combating cancer and promising avenues of research highlighted the lectures of 5 newly minted Gairdner International Award winners at a University of Toronto symposium Oct. 25–26.
The culmination of a nation-wide lecture series, the symposium also featured a dozen addresses by past Gairdner winners around the themes of “Advances in the Treatment of Cancer” and “Advances in Our Understanding of Cancer.” Established in 1959 by Toronto businessman James Gairdner, the awards aim to recognize research that improves the quality of life.
The 5 new winners, each of whom received $30 000 and a La Coeur statue, sketched the research that underpinned their careers and their thoughts on where their fields are headed. The 2007 recipients:
David Allis: “K” for cancer
Honoured for his work in cancer epigenetics, the head of the Laboratory of Chromatin Biology at Rockefeller University in New York City, New York, said in his lecture that he was struck by the concept of identical twins having the same DNA, yet only 1 with autism. That notion, to Allis, seemed a powerful demonstration that DNA cannot explain all changes in gene function.
The theoretical pair of twins demonstrates that genes can remain unchanged, but suddenly “switch off” when they should remain active. Epigenetics, Allis's specialty, aims to determine how to turn these genes back on.
Allis discovered a “K” marker that may be a cancer switch inside histone tails in DNA sequences. Based on that discovery, a Sloan-Kettering study applied drugs to a lung cancer patient and discovered that his tumours hollowed out after 8 weeks of treatment (J Clin Oncol 2005;23[17]:3923-31).
Kim Nasmyth: Chromosome tug-of-war
Cited for decoding the mechanics of cell division, the Whitley Chair holder at the Department of Biochemistry at Oxford University in England spoke of his team's efforts to track DNA during separation.
A cell must line up all 46 chromosomes in its nucleus before separating. An enzyme called cohesion holds the chromosome pairs inside a protein ring until the moment when they are all aligned and another enzyme, dubbed separase, kicks in. Intrigued by how DNA got inside the cohesion ring, Nasmyth found that the cell twists open a hinge on 1 side of the ring to allow the DNA to enter.
Cohesion also seems to have other uses besides cell division. A lack of cohesion has been traced to Cornelia de Lange Syndrome, which affects child development, Nasmyth said.
Harry Noller: X-rays mark the spot
Awarded for his pioneering work in x-ray imaging, the director of the Center for Molecular Biology of RNA at the University of California, Santa Cruz, California, used animation to illustrate his efforts to map ribosome structure.
A mass of what appears as unraveled, tangled videotape sits inside our cells. Noller's team mapped that enzyme, called a ribosome, to unprecedented detail using x-rays, in hopes of understanding how it decodes RNA — nucleic acids that are associated with the cell's chemical activities.
Noller said the ribosome moves in concert with the movements of RNA through its massive structure. The team hopes to completely map the process.
Thomas Steitz: Drugs target the spot
Building on advances in the knowledge of ribosome structure, the professor at the Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute at Yale University in New Haven, Connecticut, outlined how awareness of the process can help in the design of less resistant antibiotics.
A class of antibiotics called macrolides, for example, bonds in a peptide tunnel inside the ribosome, Steitz said. Different families of antibiotics bind to different areas in the ribosome. Thus, a researcher can take a piece of 1 antibiotic, bond it to a piece of another, and make a hybrid that binds to the ribosome more tightly and combats antibiotic resistance.
Dennis Slamon: Different breasts, different cancers
Sketching advances in breast cancer research, the professor of the Department of Medicine at the University of California at Los Angeles said it was once believed all breast cancers were of similar composition and should receive similar treatments. But research indicates that more molecular information about cancer should lead to more effective — and less invasive — therapy for patients, Dr. Slamon said.
Slamon was honoured for discovering, in 1989, that 20% to 25% of breast cancers have an overactive hormone called HER2. He targeted the hormone using herceptin, in combination with chemotherapy, and found it improved the survival rate of cancer patients in the first year after therapy.
Burning up tumours
Among the addresses from former Gairdner recipients and other prominent medical researchers was 1 from Tak Mak, the director of the Campbell Family Institute for Breast Cancer Research and Senior Scientist at the Division of Stem Cell and Development Biology, Advanced Medical Discovery Institute/Ontario Cancer Institute. It tackled the so-called oncogene revolution.
Mak argued that the revolution set back clinical oncology. In 1976, he said, researchers had a dream: to cure cancer by blocking oncogenes. Some inhibitors have been in trials for more than a decade, but with limited success, he said.
Instead, Mak suggested targeting metabolism as the basis for a new anticancer strategy and cited his recent work using diachloroacetate in mice, which appears to suppress tumour growth (Science STKE, 10 April 2007, p. pe14).