Cancer :: Cancer Tumor Survival During Radiation Therapy

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-1a 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-1a 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-1a 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-1a 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.

HIF-1a has been known to play important roles in development, physiology, and pathological processes such as cancer, cardiovascular disease and inflammatory response. So far, more than 60 genes have been identified as direct targets of HIF-1a including genes involved with angiogenesis (blood vessel generation), metabolic adaptation, and invasion, or metastasis. According to the authors, the interaction between nitric oxide and HIF-1a 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.

?This could result in a new way to treat tumors,? added Li. ?The next phase of research would be to find chemicals that can block HIF-1a activation or inhibit protein synthesis of nitric oxide. The good news is that there are a lot of drugs out there that already work by inhibiting enzymes and proteins.?

Other institutions involved with this study included the University of Louvain Medical School in Brussels, Belgium, Duke University Medical Center, West China Second University Hospital and First People?s Hospital in Shanghai, China.

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