Top Scientists Gather to Address Metastasis, Cancer's Prime Threat, and to Honor Leading Researcher Isaiah J. Fidler
M. D. Anderson News Release 03/21/07
An international blue-ribbon group of cancer researchers gathers in Houston this week to focus on metastasis - the deadly spread of disease from a primary tumor to other organs that causes the vast majority of cancer deaths - and to honor a colleague who is a research leader in the field.
Competitors, colleagues, friends, and top experts in cancer research will honor Isaiah J. Fidler, D.V.M., Ph.D., professor and chair of the Department of Cancer Biology at The University of Texas M. D. Anderson Cancer Center during a symposium March 23-24 at the Houston Marriott Medical Center.
"Much of what we know about the fundamental biology and mechanisms of metastasis comes from the laboratory of Dr. Josh Fidler. His basic and translational research have profoundly altered the direction of cancer therapy," says M. D. Anderson Cancer Center President John Mendelsohn, M.D. "The astounding list of speakers for this symposium is perfectly fitting recognition of his contributions to cancer research."
In landmark findings, Fidler and colleagues demonstrated that 99.99% of cancer cells that depart a primary tumor die, with metastases originating from less than .01% of cells and even arising from a single cell.
Metastatic cells are not the product of random chance, Fidler found, but rather exist in the genetic diversity of the original tumor and are uniquely suited to spread and grow. A metastatic cell is like a "decathlon athlete," he notes, that must overcome 10 separate hurdles to escape its main tumor, run a gantlet of biological hazards, settle in the welcoming microenvironment of another organ, and thrive there.
Fidler revived the "seed-and-soil" hypothesis of metastasis, an insight by 19th Century British physician Stephen Paget that lay dormant for nearly 100 years before Fidler's work confirmed it. While metastatic "seeds" of a given cancer land in the fine blood vessels of many organs, they only take root and grow in certain organs with a welcoming microenvironment - the "soil" for that cancer. Prostate cancer, for example, metastasizes mainly to bones.
"So it's not enough to attack the seeds, which may be resistant to treatment anyway. We must also attack the soil," Fidler says. In most instances, this attack centers on the blood vessels that metastatic cancers weave in their new microenvironment. Fidler's research in recent years has focused on multiple therapies to send against the tumor and its new environment, with an emphasis on prostate and pancreatic cancer.
Mendelsohn says the symposium, titled Forty Years of Metastasis Research: A Symposium in Honor of Dr. Isaiah J. Fidler, will be "the definitive review of the problem of metastasis in a microenvironment."
Among the first day's speakers are:
- M. Judah Folkman, M.D., of the Children's Hospital of Boston and Harvard Medical School, who founded the field of angiogenesis, understanding of new blood vessels that nourish tumors;
- Robert Weinberg, Ph.D., of the Whitehead Institute for Biomedical Research at Massachusetts Institute of Technology, who discovered the first oncogene and will discuss the genetics of metastasis;
- Lynn Matrisian, Ph.D., of Vanderbilt University Medical Center and the leading expert in the role of proteins known as matrix metalloproteinases in metastasis;
- Harold Dvorak, M.D., of Beth Israel Deaconess Medical Center and Harvard Medical School, who first presented the idea that tumors are "wounds that don't heal," on tumor vasculature;
- Adrian Harris, M.D., Ph.D., of Oxford University, on oxygen deprivation and tumor angiogenesis;
- and Richard Hynes, Ph.D., Howard Hughes Medical Institute and MIT, on the cell biology of metastasis.
"Usually you organize a meeting around a theme. This one is different, it has no theme," Fidler says, "These invitees are all teachers, leaders in their own classrooms, if you will, and the field of metastasis is a big school. We don't want to limit our discussion to just a few classrooms.
"All of these people, at one time or another, I have been able to argue with. Not fight, mind you, but argue. When scholars argue, knowledge is gained," Fidler says. "They are also my friends, and this is very meaningful for me."
Fidler is stepping down as chair of cancer biology in September, but will remain at M. D. Anderson as a researcher. "I will be working in brain metastases mostly, because it's an unbelievable burden to the world and a tough topic," Fidler says.
While there are about 17,000 cases of primary brain cancer diagnosed in the United States each year, there are about 10 times that number of cases in which other cancers spread to the brain.
It's a difficult research field because the problem is complex and research funding is shrinking, Fidler notes. "You can't get funding unless you generate preliminary data and to generate preliminary data you need a lot of investment. I can afford to invest time and money that I've raised and saved. If it's not successful, well, it's okay for me to fail now. It wasn't okay to have failed 40 years ago, but I think I can afford it now."