To Stop Cancer: Block Its Messages

May 12, 2015

The average living cell must transmit a constant stream of messages quickly and efficiently from its outer walls to the inner nucleus. But this communication system leaves itself open to mutations that can give rise to a “spam attack” that promotes cancer. Prof. Rony Seger of the Biological Regulation Department [Weizmann Institute] and his team have now proposed a method of shutting off the overflow of information before it can get to the nucleus.

Since cells don’t have electronic communication, they use proteins. The membrane-to-nucleus communications system is known as a cellular signaling pathway, and there are about 15 different pathways. Seger has identified a number of the proteins involved, especially in one particular pathway, the MAPK/ERK cascade, which is involved in cancer.

In normal cells, the messages are delivered in spikes: the last protein in the relay slips into the cell nucleus, delivers the memo, and slips out again. But following certain mutations, the previously useful message becomes spam: It gets sent over and over, flooding the nucleus’s “inbox.” In the case of such messages as those to grow or divide, the result may be cancerous.

A crucial step in this pathway takes place when a molecule called ERK undergoes a transformation that enables it to pass through the membrane surrounding the nucleus. Seger has researched this step in depth, revealing a complex process that must occur for ERK to get its message across.

Seger realized that an effective nuclear “spam filter” on the ERK pathway would involve blocking just this step, thus preventing specific ERKs’ “messages” from getting into the nucleus. He and his group designed a variety of small molecules to block the transfer of ERK molecules into the cell’s nucleus.

The team identified one potential drug molecule that performed quite well, even causing many of the cancer cells to die. Importantly, this molecule did not affect normal cells, suggesting that it mainly targets the cancer process and therefore might have fewer side effects than the present chemotherapy drugs.

One of the cancers that the molecule eradicated in the experiments was melanoma, an often fatal cancer with few available treatments. The drugs currently used for melanoma, says Seger, usually work for a while and then the cancer becomes resistant to them. He envisions the new molecule being added to the drug regimen, in rotation with others so that resistance cannot develop.

Source: Excerpt of press release, Israel Ministry of Foreign Affairs

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