To find new cancer drug targets, reorganize kinases

Grouping protein kinases by their reaction to drugs could reveal new cancer drug targets.

Protein kinases—a class of signaling molecules—regulate most cellular processes. When protein kinases malfunction, diseases such as cancer can result. This is why certain types of protein kinases implicated in disease are desirable drug targets. A new study, however, takes a fresh approach to grouping kinases as potential drug targets.

Much of the previous research with kinases involves grouping them based on how closely related they are to each other. This method, says Markus Seeliger of the Renaissance School of Medicine at Stony Brook University, somewhat resembles cataloging artworks alphabetically by artists and has had success—such as in the case of targeting a kinase to treat chronic myeloid leukemia. However, the method also has drawbacks.

In the new study, the researchers grouped kinases by qualities related to their biological function. In particular, they grouped for the first time kinases by their response to drugs. This approach is more like how museums arrange artworks by subject or artistic period, rather than alphabetically.

By doing this, the researchers discovered why some kinases bind to more drugs than other kinases, and why some kinase mutations cause resistance to drugs.

“We found that there are surprisingly huge differences among the kinases, as some are inhibited by only a few drugs and others by many. We can also demonstrate that a specific shape in these indiscriminate kinases enables them to be this way,” explains Seeliger, an associate professor of pharmacological sciences.

He believes that this novel method of grouping kinases creates a new view on the kinase family of drug targets and may help to build a poly-pharmacological approach to drug targeting kinases that could replace the current approach of kinase-targeting drugs that has drawbacks.

The new research appears in Cell Chemical Biology. Grants from the National Institutes of Health supported the research in part. Additional researchers from Stony Brook and Memorial Sloan Kettering Cancer Center contributed to the work.

Source: Stony Brook University

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