Annual Forum 1994 – Cell Cycle Checkpoints

Chair:
Leland Hartwell, Ph.D., University of Washington, Seattle, WA

Participants:
Karen Antman, Ph.D., Columbia University, New York, NY
Fred Applebaum, MD, Fred Hutchinson Cancer Center, Seattle, WA
Steven Elledge, Ph.D., Baylor College of Medicine, Houston, TX
Gerard Evan, Ph.D., Imperial Cancer Research Fund Labs, London, England
Steven Friend, MD, Ph.D., Massachusetts General Hospital Cancer Center, Charlestown, MA
Ed Harlow, Ph.D., Massachusetts General Hospital Cancer Center, Charlestown, MA
Richard Kolodner, Ph.D., Dana Farber Cancer Institute, Boston, MA
Kim Nasmyth, Ph.D., Research Institute for Molecular Pathology, Vienna, Austria
Herbie Newell, Ph.D., Newcastle University Medical School, Newcastle- upon-Tyne, England
Patrick O’Connor, MD, National Cancer Institute, Bethesda, MD
Brian Reid, MD, University of Washington, Seattle, WA
Terry Van Dyke, University of North Carolina, Chapel Hill, NC


Layout and Goals
Sessions:

  1. Checkpoints and Transition Points
  2. Fidelity During Proliferation
  3. Tumor Development & Therapies
  4. Getting to the Clinic

Dr. Hartwell organized sessions to focus on how a cell determines whether a particular stage in the cell cycle has been completed, the mechanisms that tell a cell to stop if the stage has not been successfully completed, the phenotype of mutations in these controls, and how these controls could be used as targets for therapy.


Outcome Report
The subject of this year’s meeting was ‘Cell Cycle Checkpoints and Cancer.” Our understanding of the biology of the cell cycle has progressed rapidly in the last five years to a point where it is relevant to consider how this understanding can be used in cancer therapy.

Checkpoints play an important role both in the origin of cancer and in its potential treatment. Checkpoints constitute the “nerve center” of the cell cycle, receiving and sending messages to various cellular processes so that growth and repair can be integrated. For example, p53, the most commonly altered gene in cancer cells, coordinates signals from outside the cell and signals from the cell’s information center, the chromosomes. If the chromosomes are damages when another signal says to divide, the p53 gene either halts the cell’s progression to allow repair of the damage or, if the damage is too great, sends a signal for the cell to commit suicide. Dead cells are better than proliferating damaged cells. By eliminating the p53 gene, cancer cells evade this surveillance, producing many damaged cells that become the Frankensteins that we know in cancer.

The meeting generated lively non-stop discussion for three full days. It was an intensely educational experience for all participants. People who do not normally interact with one another were brought together in this forum: geneticists who are finding the genes that control cellular checkpoints in the ordinary baker’s yeast, a model for the human cell; scientists who are exploring the behavior of these genes in human cells growing in culture dishes; individuals who study behavior of tumor cells in animal models like the mouse; and clinicians, who treat cancer in patients.

One of the main impressions that derived from the meeting is the incredible complexity of human biology and disease. Human cells contain as many as 100,000 genes whose functions we need to learn if we are going to truly understand human disease. While we tend to think of cancer as a single disease, it is, in fact, hundreds of diseases. The encouraging side is that we now have the methods for unraveling this complexity. The discouraging side is that it will take us many decades to complete the process. Much of the discussion centered on shortcuts to eradicate the disease even before a full understanding is achieved. The most hopeful ideas at the moment involve; 1) early detection of cancer through sensitive techniques that monitor the presence of altered cancer genes in the body so that therapy can begin at a time when it is more successful, 2) searches for new therapeutic drugs that utilize drugs in combination based upon new ideas about the cell cycle.

Everyone agreed that the Forbeck Forum plays a unique role in accelerating the progress in cancer research. It is rare indeed that scientists from such diverse backgrounds gather to spend several days in constant discussion. The broadening of our vision of this disease as a result of the meeting will certainly impact how each of the participants conducts his or her research in the laboratory.