When they metastasize (leave the primary tumor and spread to other organs), cancer cells must improvise to survive and flourish under harsh conditions such as a shortage of basic nutrients like glucose. One way they do this is by reprogramming their energy-generation system, said Prof. Uri Nir of Bar-Ilan University in Ramat Gan.
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.
When the scientists searched for a similar enzyme in the mitochondria of other body cells, they found it only in sperm cells.
Nir reasons that this may be because sperm cells—the only cells that must function outside the body they came from—are similar to metastatic cells in their need to generate energy under difficult 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,” said 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,” Nir explained.
Using advanced chemical and robotic approaches, Nir’s lab team developed a synthetic compound, E260, which can be administered orally or by injection.
When introduced into metastatic cells in culture or mice with metastatic tumor, E260 enters the mitochondria and binds with the enzyme FerT, inhibiting its activity and causing a complete collapse of the entire mitochondria “power station.”
Nir said that metastatic cancer cells actually attempt to decompose and rebuild damaged mitochondria but expend a fatal amount of energy in the process.
“We have treated mice with metastatic cancer and this compound completely cured them with no adverse or toxic affect that we can see. We have also checked several normal cells and they are not affected,” reported Nir.
“Thus, E260 is a new anti-cancer agent which imposes metabolic stress and cellular death in cancer cells.”
Nir and his team plan to pursue Phase 1 clinical trials within the next 18 months.
The research was published recently in the journal Nature Communications. The authors include Nir as well as Bar-Ilan life-sciences researchers Yoav Elkis, Moshe Cohen, Etai Yaffe, Shirly Satmary-Tusk, Tal Feldman, Elad Hikri, Ariel Feiglin, Yanay Ofran and Sally Shpungin in addition to Abraham Nyska from Tel Aviv University.