Is There a Future for Anticancer Cell Cycle Kinase Inhibitors?

The present status and future hopes for the development of chemotherapeutic agents to treat cancer by inhibiting cell cycle kinases (CDKs) was reviewed in a recent journal article.

Several families of enzymes known as cell cycle kinases regulate the life cycle of normal cells. These enzymes work hand-in-hand with a class of molecules called cylins that have no enzymatic activity. The individual steps of cell division must carefully be controlled to ensure that all the required molecular components are in place before proceeding to the next step. This control ensures an orderly division of the cell with high fidelity DNA replication.

When CDK control breaks down due to molecular damage or mutation, the cell cycle may spin out of control resulting in the unregulated cell growth and division that characterizes cancer cells.

Although several molecules that inhibit cell cycle kinases have been developed and clinically screened as potential anticancer agents, none of these has been approved for commercial use, and an effective strategy to specifically control malignant cell proliferation has yet to be established. In the review published in the July 2009 issue of the journal Nature Reviews/Drug Discovery the authors discussed the potential and limitations of established cell cycle kinases as targets in anticancer drug discovery as well as novel strategies for the design of new agents.

"Future approaches should combine the lessons learned from early work using small-molecule inhibitors with the recent increased understanding of the deregulation of cell cycle protein kinases in cancer," said senior author Dr. Antonio Giordano, professor of molecular biology at Temple University (Philadelphia, PA, USA). "Chemical inhibition has emerged as a powerful approach to advance our understanding of these kinases and numerous inhibitors are being developed as potential anticancer drugs."

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