- The Washington Times - Friday, January 21, 2005

Scientists have discovered a new cancer-causing gene they believe could be an effective target for new drug therapies.

Geneticists at Memorial Sloan-Kettering Cancer Center believe the gene, dubbed “Pokemon,” could be the key cellular oncogene that when mutated or dysfunctional lead normal cells to become cancerous.

“There are a number of genes that can cause cancer, the so-called oncogenes, but Pokemon is unique in that it is needed for other oncogenes to cause cancer,” said Dr. Pier Paolo Pandolfi, the senior author of the study.

“Pokemon is a main switch in the molecular network that leads towards cancer,” Dr. Pandolfi said. “If we could turn Pokemon off, it may block the oncogenic circuitry and stall the malignant process.”

The gene could prove to be an ideal target for exploring new medicines against cancer, the study said.

Cancer, which the World Health Organization says kills 6 million people annually — an estimated 12 percent of the world’s deaths, is caused by the activity of rogue genes within cells that force them to mutate and divide uncontrollably.

Although the gene shares its name with the popular Japanese pocket monster cartoon character, Dr. Pandolfi said it is by pure coincidence. Pokemon is short for POK Erythroid Myeloid Ontogenic factor.

The New York geneticists, under Dr. Pandolfi’s supervision, found out that when they inactivated the Pokemon gene in mice through genetic engineering, the process that transforms normal cells into cancerous ones was blocked.

The next step, Dr. Pandolfi said, is to find drugs that can shut down the protein’s function, and in the same way can be a powerful anti-cancer agent.

But because his team already knows so much about the behavior of Pokemon, that should not be difficult, he added.

“We can aim at functionally blocking the activity of this protein pharmacologically in a relatively short time,” he said.

Switching off genes comes with risks, but the geneticist believes this new approach — stopping cancer before it can start — will prove less toxic than standard therapies such as radiotherapy and chemotherapy.

“Today, what we do is very simple, but unfortunately very toxic, which is to take out the tumor surgically or to attempt to kill the cells,” Dr. Pandolfi explained. “When you attempt to kill the cancer cells, you cause collateral damages: You kill cancer cells, along with — unfortunately — normal cells.”

With gene therapy, “we are going against the specific molecule which we know is the regulator,” he said. “We will reduce tremendously the toxicity because we are repairing the defect. We are not killing the cells.”

Dr. Pandolfi’s team is trying to identify the cancers in which Pokemon plays a direct role, and those in which its role is less immediate.

However, even in malignancies where its role is less clear, the gene should still be a very good target for therapy, he said.

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