Gene radiotherapy system shows promise for fighting treatment-resistant cancer cells

Jun 16 2008

A gene radiotherapy system that detects and treats cancer cells that are resistant to traditional forms of chemotherapy and radiation showed success in the laboratory and could eventually prove beneficial for cancer patients, according to researchers at the Society of Nuclear Medicine's 55th Annual Meeting.

The new system targets oxygen-deficient hypoxic cancer cells that have activated a gene known as HIF-1, which ensures the cells' survival and makes them unresponsive to most current treatments.

"These types of cancer cells pose a significant challenge in treating many patients," said June-key Chung, a professor of nuclear medicine at Seoul National University College of Medicine, Seoul, South Korea, and lead researcher of the study, Human NIS Gene Radiotherapy Targeting HIF-1 Activated Cancer Cells. "Our research shows that this system successfully targets these hard-to-treat cells in vitro. Eventually, it could offer a novel way to develop new therapies for drug- and radiation-resistant cancers."

Hypoxic cancer cells are found in solid tumors that develop in many different cancers, including cancers of the liver, breast, prostate and uterus. Solid tumors undergo a multitude of cytogenetic or genetic changes over many years, some of which may resist almost any standard therapy.

"It is well known that hypoxic cancer cells are resistant to chemotherapy and radiotherapy, therefore creating a real dilemma for cancer therapies," said Chung. "Now, we are hopeful that new therapeutic models targeting resistant cancers, which are currently under development in the laboratory, can be successfully used for treatment. The results of our research imply that this is a real possibility."

Hypoxic cancer cells do not develop adequate blood vessels to receive oxygen. Because cells need oxygen to survive, hypoxic cells instead activate the HIF-1 protein, which changes cells' metabolism and enables them to burn sugar for energy without oxygen. Traditional cancer therapies are ineffective against hypoxic cells that have activated HIF-1 because HIF-1 regulates several genes related to the resistance of conventional cancer therapy.

In their research, Chung and his team developed a therapeutic system that targets HIF-1 human liver cancer cells in the laboratory. A reporter gene was developed that would express human sodium iodide symporter (hNIS) in the cancer cells. This gene would simultaneously track the cancer cells and treat them by allowing them to absorb iodine and radioisotope more easily. To improve imaging of the cancer cells even further, researchers also engineered the reporter gene to turn fluorescent when it encountered HIF-1 liver cancer cells so they could be tracked with optical imaging techniques. The reporter gene was then injected into human liver cancer cells. The results indicated that the system not only killed hypoxic liver cancer cells, but also could eventually be useful for visualizing how HIF-1 activation occurs in these cells.

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