Computer Model Helps Pinpoint Cancer Cell Targets

Eytan Ruppin (Tel Aviv University)

Medical and computer scientists in Israel and the U.K. have developed a computer model of cancer cell metabolism, which can help predict which drugs are lethal to cancer cells. Their work was part of a research study reported online last week in the journal Nature (paid subscription required).

Many cancer drugs are now designed to target any proliferating cells in the body, including cancer cells as well as healthy cells such as hair and gut lining cells, which are essential to the body’s overall health. Thus many cancer treatments, including chemotherapy, have adverse side effects like nausea and hair loss.

The research by Eytan Ruppin (pictured left), a faculty member in Tel Aviv University’s computer science department and medical school, with Eyal Gottlieb of the Beatson Institute for Cancer Research in Glasgow, U.K., and Tomer Shlomi of the Technion in Haifa focuses on the metabolism of cancer cells. By inhibiting their unique metabolic signatures, explains Ruppin, cancer cells can be killed off in a specific and selective manner, leaving the healthy cells.

Cancer cells have a special way of metabolizing nutrients for growth and for energy, which makes cancer cell metabolism essentially different from that of a normal cell. The researchers built a computer model that reconstructs the thousands of these metabolic reactions that characterize cancer cells.

By comparing the metabolic signatures of cancer cells to a pre-existing model of normal human cells’ metabolism, the team could distinguish the differences between the two metabolic processes. The researchers could then identify drug targets with the potential to affect the specific properties of cancer metabolism.

The researchers tested their model on cells from a specific type of kidney cancer. Their computer model led them to hypothesize that a certain pathway was essential for the cancer cell’s metabolism, and using a drug to inhibit an enzyme involved in that pathway and metabolism would selectively kill the cancer cells, while leaving normal cells intact.

In an experimental study led by Gottlieb’s lab in the U.K., the researchers were able to demonstrate in mouse and human cells that inhibiting this specific enzyme interrupts the metabolism of the targeted kidney cancer cells, thus killing them off. At the same time, similar cells lacking the specific pathway were spared.

While this model was built to simulate a specific type of kidney cancer, Ruppin believes this method can be applied to create models for other types of cancer. “This is the next big challenge for us,” says Ruppin. “We are going to continue to build models for other types of cancer, and seek selective drug therapies to defeat them.”

Read more: Candidate Drug Starves Cancer Cells of Energy Source

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