WASHINGTON--Three internationally renowned scientists received the 1997
General Motors Cancer Research Foundation Science Awards for their groundbreaking
discoveries. Each of the award winners was given a gold medal and a $100,000
prize during ceremonies held at the Library of Congress.
Herman D. Suit, MD, PhD, Andres Soriano Professor of Radiation Oncology
at Massachusetts General Hospital and Harvard Medical School, won the Charles
F. Kettering medal for outstanding contributions to the treatment of cancer.
The Charles S. Mott medal for outstanding research in cancer causation
or prevention went to M. Judah Folkman, MD, Julia Dyckman Andrus Professor
of Pediatric Surgery, Harvard Medical School. Paul M. Nurse, PhD, director-general
of the Imperial Cancer Research Fund in London, received the Alfred P.
Sloan, Jr., medal for his basic science contributions to cancer research.
The awards are named after former General Motors executives. The Foundation
awarded its first prizes in 1979. Since then, 73 scientists have shared
awards or won an award on their own.
Avoiding Amputation in Sarcoma
In 1959, when Dr. Suit began his work on sarcomas at what was then the
M.D. Anderson Hospital & Tumor Institute, 60% to 70% of patients with
malignant tumors of the soft tissue of an arm or leg lost the limb to amputation.
Today, thanks to Dr. Suit's pioneering work, "virtually all patients
with soft tissue sarcomas in their extremities are able to avoid amputation
by treatment with radiation combined with surgery and sometimes chemotherapy,"
the General Motors Foundation said in its awards booklet.
Four decades ago, radiation treatments yielded poor results. "It
was dogma that sarcomas were radiation resistant," Dr. Suit said in
his Laureate's Lecture prior to the awards ceremony.
However, Dr. Suit hypothesized that these unacceptable outcomes stemmed
from large tumor size, low radiation doses, and hypoxia (known to result
in radiation resistance) of the sarcoma cells. He tested his thesis using
"supervoltage" equipment newly installed at the M.D. Anderson
"Extremity sarcomas were treated under conditions of tourniquet-induced
hypoxia," the GM Foundation noted. The local control rate of soft
tissue sarcomas irradiated under these conditions after excision was very
high. Further, similar tumors treated under conditions of normal blood
flow did equally well.
Analysis of the first 100 soft tissue sarcoma patients managed in this
way showed that local and distant control depended upon tumor grade and
Dr. Suit continued his radiation work after moving to Harvard in 1970.
In a collaboration with colleagues at Mass General, using preoperative
radiation (50 Gy), he achieved eradication of the primary sarcoma in 90%
of patients, with good functional and cosmetic outcomes.
A study at Mass General of aggressive chemotherapy and radiation administered
prior to conservative surgery in patients with large, intermediate- to
high-grade sarcomes is now going into a larger phase II intergroup trial.
Currently, Dr. Suit is exploring the use of proton therapy in place
of standard radiation therapy, following years of experimenting with "fractionated"
doses given over a period of days. A recent analysis of this approach in
180 chon-drosarcoma and 220 chordoma patients showed 10-year tumor-free
survival rates of 92% and 45%, respectively.
Next year, Dr. Suit will help inaugurate a new proton therapy center
at Mass General, in partnership with the NCI, which will offer treatment
to patients with sarcomas and cancers of the brain, head, and neck, prostate,
and bladder, and to children with solid tumors.
Initial Skepticism on Angiogenesis
Dr. Folkman was cited for extensive contributions explaining the role
and importance of angiogenesis in tumor growth. "He realized that
the tumor and the blood vessel cells within the tumor constituted a highly
integrated and interdependent ecosystem," the GM Foundation said.
Dr. Folkman published his first paper on tumor angiogenesis in 1971.
"That paper must have been ahead of its time, because we still have
all the reprints," he quipped during his Laureate's Lecture.
When his laboratory succeeded in purifying basic fibroblast growth factor
(bFGF), the first angiogenic molecule, "there was a celebration in
our lab and skepticism outside," he said. Since then, 13 other angiogenic
molecules have been discovered by other investigators.
Dr. Folkman and his team went on to discover that malignant cells secrete
proteins that cause normally resting endothelial cells to proliferate rapidly--a
process that once turned on, stays on and feeds the tumor so it continues
to grow. Moreover, the newly dividing endothelial cells also secrete growth
factors that allow tumors cells to invade nearby tissue and metastasize.
More recently, Dr. Folkman discovered angiostatin and endostatin, the
two most powerful inhibitors of angiogenesis known and, he said, the most
powerful anticancer drugs ever tested in animals.
"Angiogenesis therapy has now moved from the laboratory into the
clinic," the GM Foundation said. Eight angiogenesis inhibitors are
now under investigation in more than 100 clinical trials in the United
States and the United Kingdom. Chief among them is the first angiogenesis
inhibitor discovered in Dr. Folkman's Laboratory, TNP-470.
Dr. Nurse was cited both for his discovery of the first cyclin-dependent
kinase and for demonstrating its role as the prime regulator of the cell
"Dr. Nurse identified genes for several important regulators of
cyclin-dependent kinases, and thereby helped to characterize the network
controlling entry into cell division," the GM Foundation said. "His
research contributed greatly to the understanding of the altered cell-cycle-control
pathways found in cancers."
His work includes demonstrating that the basic mechanism by which human
cells control progression through the cell cycle is closely akin to that
in yeast. In cancer cells, he found that cyclin-dependent kinases are activated
incorrectly and that this may cause premature mitosis and cell division
before all chromosomes are properly replicated and separated. As a result,
genetic damage may occur and accelerate the advancement of cancer.
"The work that Dr. Nurse initiated has become of great interest
to many laboratories around the world," the GM Foundation said. Scientists
are studying the genes that control cyclin-dependent kinases and the different
types of cyclin-dependent kinases and their functions. "It is hoped
that this area of study will provide a new understanding of cancer and
possible targets for future cancer therapies," the Foundation said.