TEL-AVIV — Scientists at Bar-Ilan University in Israel successfully targeted and rendered inert the enzyme that metastatic cancer cells need to survive in the body once they have left their host tumor. The findings of Professor Uri Nir, of the Mina and Everard Goodman Faculty of Life Sciences at Bar-Ilan University, and his team could pave the way to therapies that prevent metastasis, or the spreading of cancer cells from their point of origin.
Nir and his team discovered the existence of an enzyme, FerT, in the mitochondria of cancer cells that is not present in those of normal cells (mitochondria are the “power generators” of a cell). Once free within the body, metastatic cancer cells face an environment short on the nutrients, such as glucose, needed to survive and grow; FerT kicks the cancer’s mitochondria into high gear to produce energy when the given environment lacks the necessary metabolic components for survival. Basically, it makes mitochondria do more with less. Interestingly, this is what FerT does in another cell that must survive outside its origin: sperm.
“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,” explains Nir. “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.”
With this information, Nir developed a compound dubbed E260. When applied to metastatic cells in culture or mice with metastatic tumors, E260 enters the metastatic cells and then the mitochondria, whereupon it binds to FerT, distorting its energy-generating activity to such a degree the mitochondria effectively shuts down. Metastatic cells are notoriously tenacious; they can detect damage to their mitochondria and even take steps to repair them. Nir found that E260-applied cells did not have the energy necessary to both repair mitochondrial function and maintain other cell processes at the same time. The result: cell death.
More promisingly, “We have treated mice with metastatic cancer and this compound completely cured them with no adverse or toxic effect that we can see. We have also checked several normal cells and they are not affected,” says Nir.
E260 came about from the fact that cancer can most often be successfully treated in its early stages when confined to one organ. While standing immunotherapy can be effective in treating the metastatic phase of the disease, only a limited number of patients fit the criteria for such. Generally speaking, once a cancer metastasizes, treatment becomes more difficult and mortality much higher.
Nir and his team hope to pursue Phase 1 clinical trials within a year-and-a-half. The research was published this month in the journal Nature Communications.