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Cell Cycle Checkpoints

November 3–6, 1994

Chaired By

 Leland Hartwell, PhD of University Of Washington

Meeting Description

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.

The 1994 Forum Chair, Dr. Leland Hartwell, was honored in 2001 with The Nobel Prize in Physiology or Medicine.

Meeting Summary

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.

Quotes from Participants
“I’m extremely excited … and there is absolutely no doubt in my mind that the experiments we will perform on this compound will be far better designed and hopefully more successful because of the information that was discussed at this year’s Forum.” -- H. Newell, Ph.D., University of Newcastle, England

“A tremendous meeting … it was a great pleasure and experience to attend. I came away with several new ideas and collaborations, and I feel very optimistic about the future.” -- Patrick M. O’Connor, Ph.D.,, National Cancer Institute, Bethesda, MD

“I found the small, informal format to be extremely stimulating: I hope you never change it as it is really unique … have initiated some studies conceived at the meeting. In fact, the first experiment is running today.” -- Richard Kolodner, Ph.D., Harvard Medical School, Boston, MA

“The meeting format was wonderful. I’ve used a similar format in two meetings since – with excellent results and always acknowledging where the format came from.” -- Fred Applebaum, MD, Fred Hutchinson Cancer Center, Seattle, WA

“I was most impressed with the concept of gathering together a small and manageable group of top scientists in a particular field of cancer research for presentations, discussion and interaction. Remarkably the reality was even better than the concept … the interchange of ideas was obviously quite free-wheeling and very productive …” -- Larry Robertson, MD, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL

Forum Participants

Karen Antman, PhD
Columbia University

Fred Applebaum, MD
Fred Hutchinson Cancer Research Center

Steven Elledge, PhD
Baylor College of Medicine

Gerard Evan, PhD
Imperial Cancer Research Fund Labs

Steven Friend, MD, PhD
Massachusetts General Hospital

Ed Harlow, PhD
Massachusetts General Hospital

Leland Harttwell, PhD
University of Washington

Richard Kolodner, PhD
Dana-Farber Cancer Institute

Kim Nasmyth, PhD
Research Institute for Molecular Pathology

Herbie Newell, PhD
Newcastle University

Patrick O'Connor, MD
National Cancer Institute

Brian Reid, MD
University of Washington

Terry Van Dyke
University of North Carolina

Elizabeth Yang, MD, PhD
Children's National Hospital
 Forbeck Scholar