New targets for the treatment of methotrexate resistance

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Key genes involved in the development of resistance to methotrexate chemotherapy are reported in “Networking of differentially expressed genes in human cancer cells resistant to methotrexate”, a research article recently published in Genome Medicine.

Carlos Ciudad and colleagues used networking analysis of genes mutually deregulated between seven different cancer cell lines to show that DKK1, UGT1A and EEF1A1 play key roles in methotrexate resistance.  Excitingly, the application of small interfering RNA (siRNA) specific to these genes re-sensitized the tumor cells to this drug, indicating a potential treatment for chemotherapy resistance.

siRNA is an agent that interferes with gene expression and could in theory silence any specific gene of choice. Its potential as a therapeutic agent was first suggested several years ago, and some siRNA-based drugs have now even reached the clinical trial stage.  The potential roles of this technology in disease therapy are wide-ranging, and the identification of prospective genes which could be targetted with siRNAs to prevent or even reverse a cancer’s resistance to chemotherapy will be of great benefit in the future.
 
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Rebecca Furlong
Assistant Editor, Genome Medicine