M. D. Anderson’s Fidler and Roth Elected AAAS Fellows
Landmark research in metastasis - how cancer lethally spreads from a primary tumor -- and pioneering work in gene therapy have earned two scientists at The University of Texas M. D. Anderson Cancer Center elite recognition by their peers.
Isaiah J. Fidler, D.V.M., Ph.D., professor and chair of M. D. Anderson’s Department of Cancer Biology, and Jack Roth, M.D., professor in the Department of Thoracic and Cardiovascular Surgery, have been elected Fellows of the American Association for the Advancement of Science.
Jack Roth, M.D.
Jack Roth, M.D.
The AAAS announces election of new fellows in today’s (Oct. 26) edition of the organization’s prestigious journal Science. New fellows will be inducted in a ceremony on Feb. 16, 2008 at the AAAS annual meeting in Boston. Founded in 1848, the AAAS is the world’s largest general scientific society.
Nominations are offered by at least three existing fellows in one of the association’s 24 sections, or by the section’s steering group, or by the AAAS chief executive officer. The steering groups review nominations and send a final list to the AAAS Council for a vote.
“Peer recognition at this level reflects the innovative, high-impact research conducted by Dr. Fidler in metastasis and Dr. Roth in gene and molecular therapy. We are delighted to see them earn this well-deserved honor,” says Raymond DuBois, M.D., Ph.D., M. D. Anderson provost and executive vice president who was elected as an AAAS Fellow in 2004.
Both first engaged cancer as surgeons - Fidler as a veterinary surgeon - and then chose to delve into the molecular and genetic details of the disease.
Isaiah J. Fidler: Attacking the Seed and the Soil
Fidler’s research uncovered much of the fundamental biology of metastasis, the culprit in 90% of cancer deaths, and also highlighted the need to interfere with metastatic cancer’s ability to hijack normal biological processes to fuel its growth. 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, even from a single cell.
* Showed that metastatic cells exist in the genetic diversity of the original tumor and are uniquely suited to spread and grow. Like a “decathlon athlete,” they must overcome at least 10 separate biological hurdles to escape the main tumor, run a gantlet of hazards, and then settle in the welcoming microenvironment of another organ.
* Revived the “seed-and-soil” hypothesis of metastasis, an insight by 19th Century British physician Stephen Paget that lay dormant for nearly 100 years. 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.
“It’s not enough to attack the seeds, which may be resistant to treatment to begin with. We must also attack the soil,” Fidler says. In most instances, this attack requires multiple therapies and targets new blood vessels that metastases weave to fuel their growth.
Fidler has launched a new research effort in brain metastasis. There are about 165,000 cases each year of another type of cancer spreading to the brain, but only a handful of labs studying the problem, Fidler notes.
“I share the honor of this recognition with all of my fellows and colleagues and am indeed very honored to be elected an AAAS fellow,” he says.
Jack A. Roth: Delivering Tumor-Suppressing Genes
As a surgeon specializing in lung and esophageal cancers, two especially lethal forms of the disease, it became apparent to Roth years ago that there had to be a better way of treating patients.
“It was clear that surgery alone was not the answer, nor were chemotherapy and radiation,” Roth recalls. “Results were poor and side effects common. Research by us and many others showed that loss of function by tumor-suppressor genes was a major culprit in the development of lung cancer. It seemed possible to me that replacement of those genes could result in a therapeutic benefit with reduced side effects.”
While execution of the idea turned out to be far from simple, Roth and colleagues have moved gene therapy into clinical trials for a variety of cancers. His research first focused on restoring expression of p53, a cancer-suppressing gene that is damaged or missing in many cancers.
Roth was the principal investigator for the first tumor suppressor gene therapy clinical trials approved by the National Institutes of Health Recombinant DNA Advisory Committee and the U.S. Food and Drug Administration (FDA), after showing the feasibility and efficacy of this treatment in preclinical studies. Roth and colleagues:
* Were among the first to show that restoration of function for a single normal tumor suppressor gene could mediate regression of human cancers in vivo.
* Identified and characterized a number of novel tumor suppressor genes on chromosome 3, including FUS1, in collaboration with The University of Texas Southwestern Medical Center.
* Found that systemic delivery of tumor suppressor genes using a nanoparticle vector could cure mice with disseminated human lung cancer. This was the basis for the first systemic (intravenous) use of this vector and the FUS1 gene to treat human cancer, which is being tested in a Phase I clinical trial
A p53-based therapy that is injected into tumors has advanced through a phase III clinical trial for head and neck cancer and is being tested in other cancers in phase II and phase I trials. Roth co-founded Introgen Therapeutics, an M. D. Anderson start-up biopharmaceutical company now publicly traded via NASDAQ, which is advancing these therapies through clinical trials.
“For all honors like election as an AAAS fellow, it is very important to emphasize that the achievements being recognized are the result of collaborations with hundreds of outstanding scientists, clinicians and staff across institutions,” Roth says. “Gene therapy progress has been slow, with lots of technical and scientific hurdles to overcome. But there has been progress.”
Other AAAS Fellows at M. D. Anderson are: Waun Ki Hong, M.D. professor of head and neck medical oncology and head of M. D. Anderson’s Division of Cancer Medicine; Margaret Kripke, Ph.D., professor of immunology, special advisor to the provost and recently retired executive vice president; Robert C. Bast Jr., vice president for translational research; Louise Strong, Ph.D., professor of cancer genetics; and Emil J. Freireich, M.D., professor in the office of the provost.
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