Bar-Ilan prof eyes enzyme in cancer cell spread

Cancer can most often be successfully treated when confined to one organ. But a greater challenge lies in treating cancer that has metastasized, or spread, from the primary tumor throughout the patient’s body. Although immunotherapy can be effective in treating the metastatic phase of the disease, it is still applicable to a limited number of patients.

Professor Uri Nir of Bar-Ilan University in Tel Aviv and his team have identified an enzyme that supports the survival and dissemination of metastatic cells, and developed a synthetic compound that targets it and kills the cells in mice with cancer. Their research has been recognized by Israel21C as the number 1 Scientific Breakthrough in Israel.

Cancer cells that leave the primary tumor appear to possess greater tools to survive in harsh conditions. Nir and his team identified an enzyme called FerT in the energy-generating mitochondria of metastatic cancer cells.

When they targeted FerT in lab mice, the malignant cells were sapped of energy and soon died. The team then began searching for the enzyme elsewhere in the body. They detected it in only one specific cell — none other than sperm cells.

This was in important finding for Nir. “Sperm cells are the only cells in our body which exert their functions outside our body,” he says. “Like metastatic cells, sperm cells are unique in that they can also generate energy under very harsh conditions. Once they have entered the female birth canal, where there is no blood supply for them, they produce and expend enormous amounts of energy under very extreme or abnormal conditions.

“We found that very aggressive metastatic cancer cells looked for and identified this sperm-specific protein, learned how to produce it and harnessed it in order to potentiate their mitochondria and produce energy under very harsh conditions.”

Using advanced chemical and robotic approaches, the team developed a synthetic compound called E260, which can be administered orally or by injection to animals or patients. When applied to metastatic cells, the compoundenters the metastatic cells and then into the mitochondria (“power station”).

It then binds the enzyme FerT, distorts its activity and, notably, not only inhibits its activity but causes a complete collapse of the entire mitochondria power station.

“Metastatic cells are very capable,” says Nir. “When they identify the damage to the mitochondria power station, they start to activate a recycling process aimed at decomposing and rebuilding mitochondria. But this recycling process requires a lot of energy and this ongoing energy consumption leads to a severe energy depletion, metabolic crisis and death of the metastatic.

“We have treated mice with metastatic cancer and this compound completely cured them with no adverse or toxic affect. We have also checked several normal cells and they are not affected.”

Nir and his team plan to pursue Phase 1 clinical trials in the next 18 months. If successful, this discovery may result in new and innovative treatments for cancer patients worldwide.

Source: Bar-Ilan University