Overcoming Drug Resistant Tumors

A team of British scientists has reported important new information about the way cancer cells build up resistance to drug treatments. Their research could lead to way to new drugs that will prove much more effective against the most hard-to-treat tumors.

Writing in the European Molecular Biology Orientation Journal, Professor Chris Higgins of Imperial College in London and colleagues noted that many cancers initially respond to chemotherapy drugs and radiotherapy, but later develop ways of protecting themselves from the effects of treatment. One way they achieve this is by pumping out anti-cancer drugs as quickly as they arrive.

Higgins' team appears to have discovered the structure of one of the most important molecular pumps involved in this process. They hope this finding will lead the way to new anti-cancer drugs that specifically block the action of this pump.

"Without the ability to get rid of anti-cancer drugs," said Higgins in a statement, "tumors would once again be vulnerable to attack."

The pump, a molecule called P-glycoprotein, is present in small amounts in healthy tissue, where it plays a role in normal cell metabolism. But some cancer cells have high amounts of P-glycoprotein, which apparently is what allows them to expel anti-cancer drugs.

The researchers noticed that the molecule's 3-D structure changed at different times during its pumping action-similar to the moving parts of a miniature machine. "If we could understand and then disrupt the machine's mechanism, we would have an effective way of knocking out the pumping action," added Higgins.

SOURCE:

European Molecular Biology Organization Journal, October 15, 2001; 20(20): 5615-5625

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