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Researchers discover anti-cancer treatment to protect heart cells

Anti-cancer treatments kill body cells and weaken patients. So, Rutgers researchers have developed a way to strengthen these cells to tolerate the toxicity of such treatments.

A team of researchers in Alexey Ryazanov’s lab in the Robert Wood Johnson Medical School has discovered a way to strengthen the body’s cells to withstand current cancer treatments such as anti-cancer drugs and chemotherapy.

In high doses, treatments become toxic to the body, said Ryanzanov, a professor in the medical school. Using widely trusted drugs such as Doxorubicin can treat various cancers, but in high doses they also kill heart cells.

“Increasing the efficiency of that treatment would be to find something that protects heart cells from these toxic effects — and that’s what we found,” Ryazanov said. “It can protect heart cells, but at the same time it doesn’t protect tumor cells.”

The vulnerability comes from an enzyme named eukaryote Elongation Factor 2 Kinase, or eEF2K, he said. This enzyme is essential for selecting the sexual cells required for reproduction, such as eggs and semen.

Body cells deteriorate, accumulate damage and eventually die, but reproductive cells are essentially immortal — they transmit their genes from generation to generation, he said.

The resiliency of reproductive cells has always been a question, he said.

The secret behind their resiliency is the eEF2K — it is involved in a mechanism that suppresses protein synthesis, he said. Inhibiting this enzyme is necessary to weed out the weaker reproductive cells, making the next generation more reliable.

The human body is always prepared for mistakes, he said. An example of this is the sheer number of eggs that a woman goes through in her life — a woman is born with about two million eggs, and only one is needed to birth a child.

“If you give a person chemotherapy, it kills all of their [reproductive] cells,” Ryazanov said. “If we eliminate this enzyme, the [eggs] can be kept alive during chemotherapy.”

The research team tried eliminating the enzyme in mice, and they noticed the mice became healthier and more resistant to stress and radiation.

“It turned out that the enzyme is not important for the individual, it is important for the species to propagate. For any individual person, it’s barely detrimental,” he said. “Either way, this makes it an ideal drug target. If we inhibit it, the person will feel nothing and they will become stronger.”

Michelle Chu, one of the main authors of the study, noted that the mice they were testing showed much more bodily strength after researchers removed eEF2K from their cells.

Chu, a Rutgers alumna, said getting rid of eEF2K shows a resistance to cell death, or apoptosis.

“In the radiation treatment, mice hair usually turns gray,” she said. “The mice without the eEF2K did not have gray hair. It is essentially aging-combating.”

Right now, there are very efficient anti-cancer drugs, Ryazanov said.

The current method in developing these drugs is to target cells that regularly divide, he said. The real problem is that eliminating all cancer cells would have to occur in such a high dosage that normal cells would be killed as well.

To maximize the opportunity of this new method, Ryazanov started a company in Princeton named Longevica Pharmaceuticals. They developed a small molecule for this enzyme so it can be given together with chemotherapy, he said.

Marie Makhlina, a researcher at Longevica Pharmaceuticals, said the drug would most likely be administered through IV or direct injection. This would be done before or during the treatment to optimize its effectiveness.

If ingested orally, the stomach might digest it too quickly for it to be effective, she said.

“We’re not inventing new treatment, we’re enhancing the effects of the old treatment,” Ryazanov said. “We will protect normal cells, allowing increasing dosages of treatments.”

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