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Three Prominent Researchers Receive GM Foundation Awards

Three Prominent Researchers Receive GM Foundation Awards

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 Cancer Center.

"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 size.

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.

Cyclin-Dependent Kinases

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 cycle.

"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.

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