ANN ARBOR, Mich. When it comes to gene sequencing and personalized medicine for cancer, spotting an aberrant kinase is a home run. The proteins are relatively easy to target with drugs and plenty of kinase inhibitors already exist.
Now in a new study, University of Michigan Comprehensive Cancer Center researchers assess the complete landscape of a cancer's "kinome" expression and determine which kinases are acting up in a particular tumor. They go on to show that those particular kinases can be targeted with drugs potentially combining multiple drugs to target multiple kinases.
"We have a small but effective inventory of 'druggable' mutations that we know play a role in cancer. As we are doing more sequencing, we're coming to realize just how small that inventory is. On the one hand, it's a limitation. On the other hand, there are numerous oncogenic kinases, and there are a lot of kinase inhibitors. Our goal is to determine how to match more of these therapies with the right patients," says senior study author Chandan Kumar-Sinha, Ph.D., research assistant professor at the Michigan Center for Translational Pathology.
The researchers looked at RNA sequencing data from 482 samples of both cancerous and non-cancerous tissue and identified the most highly expressed kinases in individual breast cancer and pancreatic cancer samples. They found certain common themes.
"A lot of samples showed one or two kinases that showed an outstandingly high 'outlier' expression," says Kumar-Sinha. It wasn't that the researchers always found a mutation just that one or more kinases were expressed at a far higher level than all other kinases.
"We don't always know what's causing it to be overexpressed. But since it's there, we know that somehow the high expression of oncogenic kinases is advantageous to the cancer, and so we can therapeutically exploit that dependency," Kumar-Sinha says.
Results of the study appear online i
|Contact: Nicole Fawcett|
University of Michigan Health System