Continuous NCI Grant Fuels Radiation Oncology Research

 

(Clockwise, from left:) Dr. K. Kian Ang,

Dr. Raymond Meyn and Dr. Michael Weil examine gel slides.

The foundation for modern radiation therapy laid nearly 50 years ago by the late Dr. Gilbert H. Fletcher was recalled recently when the Division of Radiation Oncology received a $7.2 million federal grant for research.

 

"This new five-year grant extends what may be the longest continuous funding from the National Cancer Institute (NCI) for radiotherapy research. The first grant was awarded to Dr. Fletcher in 1962, and the latest will help support our comprehensive research into the year 2001," notes Dr. James D. Cox, head of the Division of Radiation Oncology.

 

Called a program-project grant, it will fund four integrated research projects and three core components involving more than 50 physicians, scientists and technical staff from a dozen different disciplines. Dr. K. Kian Ang, the division's deputy head and holder of the Gilbert H. Fletcher Memorial Chair, serves as principal investigator of the grant.

 

The long-term goal of the research is to improve the complication-free cure rate of radiotherapy for the management of many cancers. Dr. Ang believes this goal can be achieved by better understanding the molecular and biochemical mechanisms of treatment failures and complications, then using that knowledge to design more effective individualized therapies.

 

Dr. Cox credits the philosophy of multidisciplinary teamwork fostered by Dr. Fletcher before M. D. Anderson was built with setting the standards that are followed today.

 

"Our current research grew out of the unique collaboration that Dr. Fletcher started with radiation oncologists, physicists, surgeons and laboratory scientists more than four decades ago. His group was at the cutting edge of translational research long before that term was coined," says Dr. Cox, who holds the Hubert L. and Olive Stringer Chair in Oncology.

A French-born physician, Dr. Fletcher joined the fledgling M. D. Anderson staff in 1948 as director of radiotherapy. He opened a basement clinic in temporary quarters of an old family estate and soon began building a model of the first cobalt-60 unit that would dramatically change the outlook for cancer patients around the world.

 

Upon moving into the permanent M. D. Anderson facilities in the Texas Medical Center in 1954, Dr. Fletcher enlarged his collaborative efforts and captured the attention of the NCI, which allocated funds to M. D. Anderson to evaluate a new 22-million electron-volt betatron. Ensuing studies demonstrated how the cobalt-60 and the betatron complemented each other. In 1962, NCI gave M. D. Anderson its first formal grant for radiation research.

 

"The long duration of NCI support for our research has been possible because of the increasingly strong and diverse laboratory investigations that link multispecialty scientists and physicians. One great strength has been extensive pre-clinical animal studies conducted in collaboration with the Department of Veterinary Medicine and Surgery," Dr. Cox says.

 

The four projects and core components funded by the grant were judged "outstanding" and "highly significant" by the NCI reviewers. The projects include:

 

· Studies on the role of apoptosis, or programmed cell death, directed by Dr. Raymond E. Meyn, professor of experimental radiation oncology.

 

More than a decade ago, Dr. Meyn and his colleagues were the first to identify the importance of the programmed cell death process in how tumors respond to radiation. From laboratory experiments, they have documented some of the biochemical and molecular mechanisms associated with apoptosis. They also have shown how anti-cancer drugs administered at specific times can enhance the rate of tumor destruction by radiation.

 

Dr. Meyn's group will work with other investigators to predict apoptosis through use of a special index that measures molecular components thought responsible for radiation resistance. They hope to develop methods to regulate programmed cell death for each patient.

 

· Research to forecast how normal tissues will respond to radiation, led by Dr. William A. Brock, deputy chairman of the Department of Experimental Radiation Oncology.

Dr. Brock's team focuses on refining laboratory tests to predict normal tissue damage that may be sustained when radiation is delivered to tumors. Studies have shown that radiation sensitivity can be calculated through analyzing the impact of radiation on normal fibroblasts, or cells found in connective tissues, which are obtained from skin biopsies.

 

Early clinical trials are under way to streamline the tests and strengthen their predictive value. An important component centers on collaborative research to determine if the side effects of combination chemotherapy given with radiation also can be anticipated.

 

· Laboratory investigations of the genetic contribution to variability in radiation injury to normal tissues, directed by Dr. Michael Weil and Dr. Elizabeth L. Travis, who are, respectively, assistant professor and professor of experimental radiation oncology.

 

Preliminary studies in mice suggest that a very small number of genes are responsible for the observed differences in radiation damage of some normal tissues. Using molecular techniques, these scientists are testing the theory that there is a specific genetic basis to explain individual variations in radiation-induced damage to normal cells. Their research results are expected to help define genes that may regulate radiation-induced apoptosis being explored by Dr. Meyn's group.

 

· Studies to improve radiation therapy through using specific anti-cancer drugs that enhance the curative effects of radiation. Co-directors of this project are Dr. Ang and Dr. Walter Hittelman, chief of the Section of Cellular Oncology in the Department of Clinical Investigation and holder of the Sophie Caroline Steves Professorship in Cancer Research.

 

Pre-clinical research demonstrated that two chemotherapeutic drugs, fludarabine and gemcitabine, could increase the tumor-killing potential of radiation when administered concurrently with radiation. New clinical trials for patients with head and neck cancers are expected to ascertain the optimal doses and timing for the combined radiochemotherapy. This project builds on the long-time collaboration with the Department of Head and Neck Surgery to offer less-radical surgery combined with more effective radiation and chemotherapy.

 

Faculty and staff participating in the research represent the Departments of Biomathematics, Cellular Oncology, Cellular and Molecular Pharmacology, Clinical Cancer Prevention, Epidemiology, Experimental Radiation Oncology, Head and Neck Surgery, Molecular Pathology, Radiation Oncology, Radiation Physics, Tumor Biology and Veterinary Medicine and Surgery.

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