In breast cancer, the researchers spotted outlier expression of ERBB2 kinase in HER2-positive tumors, which would be expected. HER2-positive tumors can be treated with Herceptin. But they also found another kinase, called FGFR4 and they found that adding a drug that blocks FGFR4, in combination with Herceptin, improved the anti-cancer effect. This was done only in cells in the laboratory, but the FGFR4-inhibitor continued to be effective in cells even after they became resistant to Herceptin.
In the pancreatic cancer samples, the researchers found several different kinases that have drugs that work against them, including MET, AKT and PLK. Pancreatic cancer is one of the most deadly types of cancer, often diagnosed in its late stages when treatments are not very effective. The main driver of pancreatic cancer, a mutation in a gene called KRAS, has proven difficult to target with treatments.
In the lab, researchers blocked the outlier kinases and found it had an effect against the cancer cells. They then blocked KRAS something that can be done in the lab but has not been achieved in patients with pancreatic cancer and found an even larger effect.
"If in the future we could target KRAS in patients and also hit the outlier kinases, it could have a huge impact on treatment of pancreatic cancer," Kumar-Sinha says.
These findings must still be tested in patients, but researchers are hopeful that targeting specific kinases expressed in an individual patient's tumor could make a difference.
The U-M Comprehensive Cancer Center is currently using gene sequencing techniques to help match advanced cancer patients with potential clinical trial opportunities based on the make-up of their tumor.
"We hope kinases will represent another available avenue with whole genome sequencing. If we can identify rational multiple targets for treatment, it's more effective. This gets us one
|Contact: Nicole Fawcett|
University of Michigan Health System