A blood test that detects proteins commonly released by a growing tumor could one day become a useful tool for monitoring the effectiveness of chemotherapy and radiation treatment in people with advanced throat cancer, according to a study published in the June 1, 2007, issue of Clinical Cancer Research. Scientists in the National Institute on Deafness and Other Communication Disorders (NIDCD) and National Cancer Institute (NCI), two of the National Institutes of Health (NIH), in collaboration with researchers of the University of Michigan, found that throat cancer patients who showed a decline in several cancer-related proteins following chemotherapy and radiation treatment were more likely to remain in remission, while those who experienced a large rise over time in those proteins frequently exhibited a return of throat cancer. The findings could help lead to the development of a blood test that enables doctors to detect the recurrence of throat cancer early on, when there is still time to pursue a second line of treatment, such as surgery or drug therapy.
In the largest long-term study of its kind, NIH and University of Michigan researchers tested the blood of 30 patients who had undergone chemotherapy and radiation treatment for advanced throat cancer. Starting immediately before treatment and continuing every three months for 12 months, the researchers tested the patients’ blood for five proteins that, in previous studies, had been found to occur at heightened levels in head and neck cancer patients. These include two cytokines known as Interleukin (IL)-6 and IL-8, and three growth factors known as growth-related oncogene (GRO)-1, vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF). These cytokines and growth factors play an important role in the body’s inflammatory response and in the growth of cells and new blood vessels. Because the researchers used a bioassay technology that can simultaneously analyze the concentrations of each protein, only a small amount of blood was required for the test.
The majority of the patients had a complete response to therapy. Patients whose blood levels of these cytokines and growth factors dropped and remained low following treatment were more likely to continue in remission. Patients who experienced large increases in protein levels were more likely to exhibit a return of the cancer or to die from it. For example, large increases in IL-6, VEGF, and HGF concentrations over time yielded a 3.8-fold, 3.0-fold, and 2.9-fold higher risk of dying of throat cancer, respectively. Patients with an increase in three or more factors were at highest risk for dying of throat cancer — more than twice as likely as patients with an increase in two or fewer factors. Finally, patients with the sharpest rises in protein levels had lower chances for survival, with patients who had a history of smoking experiencing the largest spikes. (For this reason, estimates of relative risk of death were adjusted to exclude the compounding effects of smoking.)
Because the production of these growth factors and cytokines is controlled by the same “master switch” — a regulator protein known as nuclear factor kappa B (NF-kappaB) — the researchers suggest that this protein may represent a new target for drug therapy. Drugs that help turn off NF-kappaB are currently being tested in clinical trials at NIH and elsewhere.
The researchers note that a few of the patients experienced elevations in cytokine levels related to other illnesses or injuries, and not to throat cancer; therefore, they caution that further studies are needed in larger groups of patients to confirm if this could be a useful tool to monitor for cancer, infection, or other complications. In addition, because IL-6, IL-8, VEGF, and HGF have been detected in the blood of patients with breast, cervical, ovarian, and other cancers, they suggest that this technique may have broader application in the monitoring of other forms of cancer. Further studies would need to be performed on patients with these types of cancer as well.
Message posted by: Rashmi Nemade
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