A small-molecule inhibitor of Cdc7 kinase prevents DNA synthesis and has antitumour activity, suggests a paper online this week in Nature Chemical Biology. The finding could help scientists develop methods of treating tumours with less toxicity than is associated with related anticancer drugs currently in clinical use.
One characteristic of cancer cells is uncontrolled cell division, and many widely used?and quite toxic?anticancer drugs work by interfering with later stages of DNA replication. Cdc7 works at the very early stages of DNA replication by activating a group of proteins clustered at ‘origins of replication’, thus initiating DNA synthesis.
To see if preventing the initiation of DNA synthesis would be an effective and less toxic approach to chemotherapeutics, Corrado Santocanale and colleagues identified a potent inhibitor of Cdc7. In mouse studies, the inhibitor reduced tumor size with relatively low levels of toxicity, thus validating Cdc7 as an anticancer target. This new inhibitor will also be important in investigating the role of Cdc7 in cell division and cancer.