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Apr 13, 2007

ATM Protein Is a Possible Target for Treating Certain Types of Cancers

  • Dana-Farber Cancer Institute researchers are proposing a new protein target for the treatment of cancer related to fanconi anemia (FA).

    Individuals who inherit two mutant copies of any one of about 12 genes that make the proteins of the FA pathway develop the condition, which is characterized by increased incidence of cancer and bone marrow failure, among other things. Additionally, individuals with just a single mutant copy of one of these genes are also at increased risk of developing cancer.

    Alan D'Andrea and colleagues show that loss of ATM function in human cell lines with a dysfunctional FA pathway caused the cells to die. The dying cells were characterized by high levels of DNA breakage, which is consistent with the fact that FA pathway proteins and ATM are important regulators of two distinct DNA repair pathways, according to the investigators. They surmise that the ATM pathway of DNA repair keeps the FA pathway–deficient tumor cells alive and that loss of this pathway results in tumor cell death.

    As FA pathway–deficient tumor cells were shown to be sensitive to an inhibitor of ATM, the scientists suggest that ATM might provide a therapeutic target for the treatment of individuals with FA pathway–deficient tumors.

    The study appears online on April 12 in advance of publication in the May print issue of the Journal of Clinical Investigation.



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