Cancer stem cells live under the microscope.
(photo credit: FROM THE LAB OF DR. BARAK ROTBLAT)
Researchers at Tel Aviv University, led by Dr. Michael Milyavsky of the Faculty of Medicine, have developed a method to identify the most dangerous blood cancer cells - the stem cells that produce the rest of the affected cells and show resistance to conventional chemotherapy. They also discovered that a potential drug called Fenrentinide is particularly effective in destroying these cells.
The significance of the findings is an important step towards eliminating cancer-causing cells and preventing recurrence in patients who have allegedly recovered.
The study was conducted by doctoral student Mohammed Yassin from Dr. Milyavsky's laboratory, in collaboration with laboratories of the University of Toronto and Harvard University. The article was recently published in the scientific journal Leukemia
"We know that cancerous tumors in general, and blood cancer in particular, are made up of a mixture of different types of cells," explained Dr. Milyavsky. "Most of these cells are not dangerous, but some of them have stem cell properties that produce other cells and are actually the ones that cause the disease."
"It is important to note that even in the blood of a healthy person there are stem cells that produce a huge amount of normal blood cells in order to replace dead cells and replenish the stock," Dr. Milyavsky added. "Going back to the cancer stem cells, they are rare cells that exhibit resistance to conventional chemotherapy, and may survive even when the patient is allegedly cured."
Dr. Milyavsky revealed that "In our research, we were looking for a way to identify and mark the cancerous stem cells, with the aim of isolating them and investigating their mechanisms of action, as a step towards finding efficient treatment."
The researchers first scanned the human genome and found several DNA fragments that are active in healthy blood stem cells. Then they examined the same segments of the cancer infected cells, and discovered increased activity in one of them.
They then isolated and characterized the same cancerous DNA segment, and found that it is a section called enhancer - a DNA fragment that binds specific proteins that are particularly active in stem cells. They attached a fluorescent protein to the segment that glows when attached to the active enhancer. In doing so, the researchers engineered a genetic sensor that identifies cancer stem cells - the only ones that contain the segment in its active state.
"We inserted the fluorescence sensor into several samples of blood cancer cells taken from patients, and found that it glowed in a small population of cells," said Dr. Milyavsky. "We then isolated the glowing cells and compared them to other cells of the samples to identify what distinguishes them."
The researchers found that the glowing cells, which marked the cancer stem cells, were more resistant to chemotherapy and even produced the disease much more efficiently when implanted in mice without an immune system.
The researchers did not stop there, and decided to examine the effect of several molecules, considered to be potential medication for cancer, on stem cells that were isolated from blood cancer. They found that a specific molecule called Fenrentinide, which has low toxicity to healthy cells, is particularly toxic to blood stem cells.
"Our findings may serve as a basis for developing an effective and targeted medication for blood cancer stem cells that often survive normal chemotherapy," concluded Dr. Milyavsky. "The destruction of these cells will greatly reduce the chances of the disease reappearing, and the method we have developed for isolating the cancer stem cells may promote personalized medical approaches in the future: Using our fluorescent sensor, cancer stem cells can be isolated in a patient's blood, learn about their properties, and implement a more effective treatment for the patient."
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