Synthetic Molecules

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Two researchers at Hebrew University of Jerusalem have designed synthetic molecules that may have future implications for the development of a new family of anti-cancer drugs.

The researchers successfully reduced and even removed the growth of human malignant tissues in mice, without any toxic effects on normal tissue.

This work, by Dr. Arie Dagan and Prof. Shimon Gatt of the Department of Biochemistry of the Hebrew University-Hadassah Medical School, won the Kaye Award for Innovation during the 71st meeting of the Hebrew University of Jerusalem Board of Governors.

These molecules greatly influence the metabolism of various sphingolipids and consequently those of cancer cells. Sphingolipids are a family of complex lipid molecules that are involved in signalling pathways that arbitrate cell growth, differentiation and death.

A number of the most active molecules developed by Dagan and Gatt are derivatives of ceramide (a member of the sphingolipid family), which initiates programmed cell death (apoptosis) in a variety of cancer cells.

Usually, the levels of ceramide in cancer cells are quite low to induce a therapeutic effect. However, in preclinical studies till date, many treatments with the synthetic molecules led to increased ceramide levels in cancer cells, thereby causing their death by apoptosis. Besides, these synthetic molecules appear to be synergistic with chemotherapeutic drugs.

The researchers said that their studies showed that their synthetic compounds significantly reduced the sizes of pancreatic, prostate and breast tumors with little or no effects on normal cells and tissues.

In their view, this is a precursor to the development of a new generation of anti-cancer drugs that induce, selectively, apoptosis only to tumorous cells. These drugs are expected to be highly effective while inducing fewer side effects than current anti-cancer drugs.