Apr. 11, 2002 STANFORD, Calif. - Researchers at Stanford University Medical Center have been spreading colds to cancer patients, all in the hope of curing a deadly disease. In the unusual technique, doctors inject a modified cold virus into the liver as a way to kill cancerous cells.
The major benefit of treatment with a modified cold virus is its ability to target cancer while leaving normal cells unharmed. "We want to kill the tumor but not at the expense of the patient," said Daniel Sze, MD, PhD, assistant professor of radiology at Stanford. Sze will present his findings April 8 at the Society of Cardiovascular and Interventional Radiology annual scientific meeting in Baltimore.
Thirty-five cancer patients received various doses of the live virus, which was genetically weakened so that it was not as infectious as a normal cold virus. The patients suffered flu-like symptoms for about a week - minor side-effects when compared to the nausea, weakness and hair loss that results from chemotherapy. Of the 28 patients who received the highest virus dose, each was expected to live only about six months but instead survived closer to a year. Many of their tumors also appeared to shrink and stopped producing abnormal, tumor-associated proteins.
Sze said follow-up studies with more participants will provide a better idea of exactly how effective the treatment may be. "In this trial, we got a hint that it might actually benefit people with cancer," he said, adding that in this phase I study, the main concern was showing that the treatment is safe.
Sze and his colleagues tested their cancer-targeting cold virus in liver tumors that had spread from an original tumor in the colon, although Sze added that the virus is also being studied as a potential treatment for head and neck, ovarian, and pancreatic cancer. Colon cancer is the third-leading cause of cancer death in the United States, and most of those 50,000 annual deaths occur when the primary cancer spreads from the colon to the liver - not simply from the colon cancer alone.
To place the modified virus in the right location, Sze and his colleagues injected it directly into an artery leading to the liver. The virus then spread throughout the organ, eventually reaching every cancerous cell. Sze said if he injected the virus into a vein in the arm - or if a cancer patient simply caught a normal cold - only a miniscule amount of virus would reach the tumor. Injecting into the artery, however, concentrates the virus where it is needed.
Once in the liver, the modified virus appears to work by taking advantage of a common genetic defect in cancer cells, specifically infecting those cells while bypassing normal cells. Sze said that in about one-half to two-thirds of all cancers, a protein called p53 is defective. "P53 is like a DNA spell checker," he explained. "If it finds typos, it shuts down replication." And if the typo can't be repaired, p53 commands the cell to commit suicide.
In cancerous cells with a defective p53, the cells continue to divide despite a buildup of harmful mutations - or typos - in the DNA. By releasing the brakes on replication, cancer cells can divide aggressively, but these uncontrolled cells have an Achilles heel, Sze said. P53 would normally prevent the modified virus from entering and replicating. With no p53, these aggressive cancer cells lack a defense against the virus.
While researchers understand how the virus kills cells in a test tube, it's still an open question how it kills cancer cells in human patients, but Sze believes the immune system is involved. The tumors swell after being infected by the virus - a hallmark of immune system involvement - and high levels of immune system hormones appear after treatment. In the next round of trials, Sze hopes to better clarify how the treatment works, along with determining which tumors it most effectively fights.
Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at http://mednews.stanford.edu.
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