Prof. Shimon Gatt (left) and Dr. Arie Dagan in their laboratory at the Hebrew University. (Hebrew University photo by Sasson Tiram)A new weapon in the fight against cancer may soon be added to the global arsenal. Two Israeli researchers were awarded the Kaye Award for Innovation last week, for having designed synthetic molecules that succeeded in reducing and even eliminating the growth of human malignant tissues in mice, while having no toxic effects on normal tissue.
The underlying principle of the new therapy is inducing cell death in the abnormal cells through the use of sphingolipids, a family of complex lipid molecules involved in the signaling pathways that mediate cell growth, differentiation and programmed cell death (apoptosis). This means, in layman’s terms, that the next generation of cancer drugs could reach the long sought-after goal of forcing rogue cells to die.
Sphingolipids were named after the sphinx in Greek mythology in 1874 by researcher Johann Thudichum. The metaphor is apt: several of the most active molecules developed by Hebrew University of Jerusalem researchers Prof. Shimon Gatt and Dr. Arie Dagan are derivatives of ceramide (a member of the sphingolipid family) and – like the woman-lion sphinx, who devoured all those who could not answer her riddles – ceramide can induce apoptosis in certain cancer cells.
While the natural levels of ceramide in cancer cells are generally too low to induce a therapeutic effect, in preclinical studies to date, various treatments with the synthetic molecules resulted in an elevation of ceramide levels in cancer cells, thereby leading to death by apoptosis.
According to Dagan and Gatt, their studies demonstrated that the synthetic compounds considerably reduced the sizes of pancreatic, prostate and breast tumors with little or no effects on normal cells and tissues. In addition, their synthetic molecules appear to be synergistic with chemotherapeutic drugs.
Yissum, the technology transfer company of the Hebrew University, licensed the technology to BioLineRx, a publicly traded, clinical stage drug development company.
The drug is now in the initial testing phase, says Morris Laster, CEO of BioLineRx, “to make sure the results are as they say. There are other models like this already in development. But the data was compelling enough for our scientific advisory board to accept it,” he tells ISRAEL21c.
BioLineRx works by partnering with researchers, universities and biotech companies to further the development of promising compounds using a proprietary selection process, to evaluate a compound’s potential for success by looking at its technological novelty, patent status, market need and approvability.
“We started working on it a few months ago and right now its in vivo testing on a few different animal models,” says Laster. “The first step was to manufacture the material in our labs in Har Hotzvim. We then tested some of the derivatives for toxicology and maximum tolerated doses. Simultaneously, we tested it on cell lines of various cancers to see which one responded best to the compound, then we took the cell lines that best worked in vitro and began in vivo testing.”
The company expects to receive results within the next month or two. If all goes well, it will go into full preclinical development.
Even if the molecule fulfills its promise, however, there is still a long way to go, Laster warns. But the development of next generation anti-cancer drugs is definitely underway. There won’t ever be a universal cure, he says, but there will be a range of new therapies – hopefully including those that induce apoptosis only to tumorous cells.
“There’s no magic bullet to cancer,” explains Laster. “The thing is to develop an armory of weapons, and keep adding to it. That’s what’s important.”