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Massachusetts Institute of Technology IDs new cancer drug target
Date:11/8/2010

ntroduce mutations into DNA. This can lead to drug-resistant tumors. Consistent with this idea, the researchers showed in a companion study that lymphomas with reduced Rev1 levels did not become resistant to chemotherapy following treatment and were much less aggressive in spreading to other parts of the body.

In that study, the researchers treated mice with the drug cyclophosphamide. At first, the drug was effective in mice whose tumors had normal and reduced Rev1, but in both groups, tumors reappeared after about two weeks. This is similar to the relapse that frequently occurs during the treatment of many human cancers.

Those relapsed tumors were then transplanted into a second group of mice. In the second group, drug treatment was strikingly more effective in mice with reduced Rev1. Those mice survived much longer 100 percent of the mice with reduced Rev1 lived for 12 days, whereas some of the mice with normal Rev1 level tumors died in two days and only 40 percent lived for 12 days. These experiments showed that reducing Rev1 levels prevented the tumor cells from acquiring drug resistance and aggressiveness when they relapse so that they can be successfully treated again.

The researchers' discoveries suggest that by inhibiting translesion DNA polymerases, it might be possible to treat difficult cancers that have proven resistant to ordinary chemotherapeutic treatments and also prevent the introduction of new mutations during chemotherapy.

In these studies, the researchers used a technique called RNA interference to block the expression of the genes that code for Rev3 and Rev1, but they were unable to shut off the genes completely.


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Contact: Jennifer Hirsch
jfhirsch@mit.edu
617-253-1682
Massachusetts Institute of Technology
Source:Eurekalert

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