Researchers identify a gene responsible for spread of cancer in the body

Researchers who are now at Georgetown University’s Lombardi Cancer Center have identified a gene that promotes metastases, the spread of cancer cells through the body. This new understanding of how cancer metastasizes, linking a gene product and migration of cancer cells, may lead to therapies to stop this spread. The results of the study are published in the May 2003 issue of the journal Molecular Biology of the Cell. An advance copy of the paper can be viewed after the embargo is lifted at http://www.molbiolcell.org/in_press.shtml

Richard G. Pestell, M.D., Ph.D. and his research team have been studying the cyclin D1 gene and the protein it produces for the past decade. Now they have found that by “knocking out” this gene, the migration of cells can be halted. The migration of cancer cells through the body is a major reason why cancer is deadly.

“Patients who do not survive their cancer, often don’t die from their primary cancer, usually they die from the spread of the disease through the body. If we can understand what causes the metastasis, then we can pinpoint new targets to block the spread of disease,” said Dr. Pestell, director of the Lombardi Cancer Center, chairman of Georgetown’s Department of Oncology and Charlotte Gragnani professor of oncology. “Since cancerous — but not normal epithelial cells — migrate, therapy targeted to cell migration would be more selective. Killing only migrating cancer cells is thus less toxic, producing fewer side effects, than current chemotherapy which targets dividing cells of all types.”

“We want to make the life journey a better one for people who have cancer,” added Dr. Pestell, “and we at Lombardi are always trying to think of new approaches. Improving the quality of life for people with cancer is key. Slowing down the disease may change cancer from a fatal disease to one that can be lived with like diabetes.”

The research was conducted at the Albert Einstein College of Medicine in New York where Dr. Pestell worked prior to joining the Lombardi Cancer Center at Georgetown.

This study was funded by the National Institutes of Health, the Susan G. Komen Breast Cancer Foundation and the Department of Defense. Co-authors of this study are Peter Neumeister, Fiona J. Pixley, Ying Xiong, Huafeng Xie, Koming Wu, Anthony Ashton, Michael Cammer, Amanda Chan, Marc Symons, and E. Richard Stanley.

In their Lombardi laboratories, Dr. Pestell and his colleagues are currently attempting to “fine tune” exactly how cell migration differs from cell proliferation so they can devise targeted drug therapy to stop the spread of cancer through the body.

They are also exploring a stealth anticancer weapon. They reported in the December 2002 issue of the journal Chemistry & Biology on initial research on a new modality called caging therapy that targets single malignant cells. Unlike taking a pill that goes to all cells in the body, caging therapy uses light beams in an extremely specific approach to eradicating individual cancer cells. These findings, as well as the developments described in the Molecular Biology of the Cell paper, hold the potential of significantly improving quality of life for cancer patients through the development of less toxic treatment options.

The Lombardi Cancer Center, part of Georgetown University Medical Center and Georgetown University Hospital, seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Lombardi is one of only 40 comprehensive cancer centers in the nation, as designated by the National Cancer Institute, and the only one in the Washington DC area.

Editorial note: The Molecular Biology of the Cell paper includes an electron microscope video of migrating cancer cells. This can be viewed from a link available at http://www.molbiolcell.org/in_press.shtml after noon on February 28.