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April 14, 2007

New Research Sheds Light on Cancer Tumor Survival During Radiation Therapy

Topics: Medicine

HIF-1α overexpression is associated with increased proliferation, which might explain the adverse prognostic impact of increased concentrations of HIF-1α in invasive cancer.

Researchers at the University of Colorado at Denver and Health Sciences Center have found that nitric oxide plays an important role in tumor cell survival following treatment with radiation therapy:

The research, published in the April 13 edition of Molecular Cell, found that cellular death after radiation treatment promotes the presence of nitric oxide which then activates the HIF-1 alpha protein - a master switch in the body that "turns on" to help cells and other tissues survive - ultimately helping the tumor survive and grow.

"What we have found is a new function where nitric oxide is generated in response to tumor cell death following radiation therapy," said Chuan Li, PhD, director of Molecular Radiation Oncology at UCDHSC's School of Medicine and co-author of the study. "With this new knowledge, we can now look to uncovering drugs that can block the nitric oxide generation, potentially stopping the activation of HIF-1 alpha and the subsequent blood vessel survival. This potentially will allow cancer physicians to kill the tumor successfully when using radiation in combination with drug therapy."

Originally thought to activate only under abnormally low oxygen conditions, the researchers found that HIF-1 alpha will also activate as a response to the presence of nitric oxide. Following targeted radiation therapy, cells in tumors begin to die resulting in an influx of macrophages - the scavenger cells from the body's immune system responsible for cleaning out the dead cells. As this happens, nitric oxide is released, signaling HIF-1 alpha to become chemically activated and stabilized, "switching on" to promote the growth of new blood vessels that then feed the tumor to keep it alive as well as rebuild the cells that have died.

Signaling molecules are typically chemicals - but in this case the signaling molecule, nitric oxide, is a gas that is involved in transmitting information between cells. These molecules are released from the cell, sending a signal to other cells and triggering a response in them. Nitric oxide is one of the few known gaseous signaling molecules important in the human body. It is used in cardiovascular function and many other body functions where blood vessel dilation may be needed as an automatic emergency response to cell stress inside the body. (Continue reading at AScribe ...)

The authors of the study say that the interaction between nitric oxide and HIF-1 alpha sheds new light on the involvement of the molecule and the master switch in tumor response to treatment as well as the inflammation process in the body. While noting that there study could result in a new way to treat tumors, such as in finding chemicals that can block HIF-1 alpha activation or inhibit protein synthesis of nitric oxide, the authors also note that there are existing drugs that already work by inhibiting enzymes and proteins. In other words, patients can be encouraged by the fact that the basis for the development of drugs to block HIF-1 alpha activation or inhibit protein synthesis of nitric oxide has already been established - the concept is both reasonable and sound.

Related: 0123 Correlation of VEGF and HIF-1 alpha Expression in Human Oral Cancer Cell Lines

Cross posted from New Hope Blog

Posted by Richard at April 14, 2007 10:51 AM

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