© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 8, 670-671,
April 21, 1999
© 1999 Oxford University Press
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Bristol Award: Fidler Honored For Metastasis Research
A would-be surgeon who has spent most of his career in laboratories, Isaiah Fidler, D.V.M., Ph.D., remains devoted to the field of cancer biology that he helped revolutionize.
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"Without serious biology, there cannot be advancement in therapy," says Fidler, the 1999 recipient of the prestigious Bristol-Myers Squibb Award for Distinguished Achievement in Cancer Research. "The clinical trials of tomorrow are based on the basic research of today. Continued encouragement of basic research is the most important issue — not an emphasis on the molecule of the day."
Fidler was honored by the New York City pharmaceutical company at an April 15 dinner there for his pioneering research in cancer metastasis, which provided the basis for much of the current understanding of how cancer cells often avoid efforts to exterminate them and spread to multiple sites in the body.
He was the first researcher to demonstrate that only a small percentage of tumor cells within a primary tumor have the potential to produce metastases — a finding that "set a course for therapeutic development in the field of cancer," according to Robert Kramer, Ph.D., vice president of oncology drug discovery at Bristol-Myers Squibb.
Fidler, who is chairman of cancer biology at the University of Texas M.D.Anderson Cancer Center in Houston, estimates that the number of cancer cells with metastatic potential might be as few as "1 in 10,000, 1 in 100,000, or maybe even 1 in 1 million." The types of cells with metastatic potential also may vary tremendously from patient to patient and tumor to tumor.
"The concept of heterogeneity is very uncomfortable for many people," he says. "It means that only a few cells in a tumor are the fatal population. When one designs therapy, one cannot focus on the primary tumor. Even if you kill 95% or more of the cells, if you don't kill the small percentage of cells that are the progenitor of fatal disease, you are not going to cure the patient."
Fidler also was the first to show that cancer metastases have a predilection for certain organs and tissues that provide a special environment that encourages cancer cells' growth and survival. His research provided the proof for a concept first espoused in the 1890s by surgeon Stephen Paget: Cancer metastases result from "the interaction of favorable seeds with a favorable soil."
The road to discovery could have taken an entirely different path, had Fidler found contentment with his initial career choice of veterinary medicine. A native of Jerusalem, he dreamed of becoming a surgeon, but societal and political considerations dictated otherwise.
"In Israel in the late 1950s and early 1960s, our education emphasized that we must return to the earth," he explained in a recent interview. "We had enough lawyers and doctors; we needed to encourage people to be farmers. I compromised. If I couldn't be a human surgeon, and I had to return to the earth, then I might as well be a veterinarian."
Fidler candidly admits he found veterinary practice unsatisfying, in large part because career success was based on economic considerations. "There is no such thing as indigent care for cats and dogs," he notes.
After a short time in veterinary practice, Fidler accepted a position as a surgical oncologist at the University of Pennsylvania School of Veterinary Medicine. However, he remained restless and became increasingly frustrated with his career because "the animals I could cure, by and large, had benign disease.
The professional satisfaction that had eluded him finally came within grasp when he received a Luther Terry fellowship, named in honor of the former United States surgeon general. He used the opportunity to obtain a doctoral degree in human pathology at the University of Pennsylvania School of Medicine.
In 1979 Fidler came to the National Cancer Institute to head the metastasis biology section. It was at NCI that he conducted the seminal work that solved many of the mysteries surrounding cancer metastasis.
"I cannot emphasize too much how influential NCI has been in my work," he said. "I conducted experiments that were on a magnitude that would not have been possible at a university. If not for NCI, I seriously doubt these experiments would have been done."
"That is precisely what should be happening at a national laboratory," he adds. "A national laboratory should encourage experiments on a scale that would not be possible elsewhere for a person working with limited resources and preliminary data."
No Regrets
However, he has no regrets about his veterinary experience.
"I don't regret it at all," says Fidler. "My knowledge of veterinary medicine has allowed me to view animals, not just as a tool for research but to really have a deep understanding of animal biology and pathology. Perhaps that is how I was able to develop mice as relevant models for the study of metastasis."
Fidler has a clear vision of what the future of cancer research and therapy should hold. Growing knowledge about the heterogeneity of cancer dictates that future approaches to therapy "will be and should be" tailored to the specific traits of an individual patient's tumor cells. Until that time arrives, cancer therapy must move increasingly toward multimodality treatment, using "everything in the therapeutic armamentarium" to give cancer patients the best chance against cancer cells that have incredible survival instincts.
To ensure the realization of individualized therapy, cancer biology must continue to receive encouragement to move forward.
"General biology is incredibly important," says Fidler. "Today we are cloning multiple genes whose function is unknown. Without the biology, what these genes do will remain a mystery. If we don't know what the genes do, how can we direct therapy against them?"
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