Saturday, September 24, 2011

Protein switch makes cancer cells self-destruct

A new method developed to fight cancer cells uses a switch to make cancer cells produce their own chemotherapeutic drug, which basically kills them from the inside. The therapy consists of two proteins joined together, which are administered to all cells, healthy and cancerous. Thereafter, the first protein serves as a cancer recognition tool, which in turn activates the second protein. After the protein switch is administered to the cells, an inactive chemotherapeutic drug is added to the mix. The second protein of the fused compound then activates the drug, killing the cell from within. If all goes well, the first protein does not recognize healthy cells as cancerous, which in turn inhibits activating the inactive chemotherapeutic pro-drug. Thereby the scientists have created a protein switch that will only turn on an internal cell killing machine when it recognizes a cancer cell. This approach is radically different from current chemotherapeutic therapies, which are often administered without specifically targeting cancer cells, causing damage in healthy cells.

Key to getting the switch to work is getting it into the cell. For this, the scientists provide the genetic code for the fused proteins, which are taken up by all cells by special transporters. The cell's own replicating machinery makes proteins out of the supplied DNA. The researchers are currently working on developing ways of administering the proteins directly. After the protein switch is produced in the cells, the inactive cell killing chemotherapy is injected. The method was tested on colon cancer cells and breast cancer cells. The first protein will recognize a protein called hypoxia-inducible factor 1α, which is produced by cancer cells. Tumors need hypoxia-induced factors for survival in low-oxygen situations. Cancerous cells will often find themselves in a state of hypoxia, as rapid and uncontrolled growth of the tissue causes decreased blood perfusion. This in turn causes activation of cellular mechanisms that promote vascularization to provide more blood flow, and thus nutrients and oxygen. 

One of the key points of cancer research is finding ways to specifically target cancer cells. There are potent chemotherapeutic therapies available, which are highly effective in killing cells. The downside is that healthy cells also get damaged. Because cancer cells are usually more unstable than healthy cells, they die faster from the toxic drug. For this reason, using low doses of chemotherapy is tolerable for the body, but also very limited and with a lot of side-effects. For a long time, so called 'magic bullets' have been hallowed as the wonder cure for cancer. By using specific antibodies, that only recognize cancer markers on the cell surface, coupled with an chemotherapeutic agent, only cancer cells can be targeted. This has, however, not yielded many new therapies yet.

The approach with the protein switch could prove to be more effective, but this is yet to be tested. Current studies have been performed in vitro, while nothing is known about the efficacy in vivo. Animal testing is said to start in less than a year's time. If the protein switch is still found to be effective, it would open the way to human testing. However, this is probably many years away.

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