Cancer Science & Therapy

Biography

Biography: Uri Nir

Abstract

The aspiration to achieve efficacious cancer targeted therapy involves   intense global R&D efforts. Blockage of fundamental processes like the unique reprogramed energy generation system of malignant cells, combined with a nano-technology approach, should offer new tools for efficient interference with cancer progression. While deciphering the energy generation systems of cancer cells we found that two related enzymes (kinases), termed Fer and FerT, which normally reside in the energy power-station-mitochondria of sperm cells, are harnessed to the reprogrammed mitochondria of cancer cells. Both enzymes potentiate the generation of energy by mitochondria in cancer cells subjected to stress conditions like nutrient and oxygen deprivation. This enables the survival of cancer cells under harsh conditions which are prevalent in solid tumors and during metastatic dessimination. To translate these findings into a novel anti-cancer therapy we have combined, synthetic-chemistry, robotic, and high throughput screening approaches, for the development of a synthetic low molecular weight compound which binds and inhibit the kinase activity of both Fer and FerT. Such a compound termed E260 was then formulated and incorporated into nano-micelles to selectively target Fer and FerT in the mitochondria of malignant cells. Notably, the formulated E260 compound selectively and very efficiently perturbs mitochondrial functioning in non-metastatic and metastatic malignant cells, thereby imposing evoking energy crisis and consequent necrotic death in cancer, but not in normal cells. The anti- cancer therapeutic  potency of the E260 formulation is also manifested in-vivo,  against metastatic human tumors derived-xenografts, elicited in mice, thus portraying it as a new potential anti-cancer drug. Accordingly, E260 is now being progressed toward FDA approval for human clinical trials.