Using blood, urine and tissue analysis of a unique mouse model, a team led by UC Davis researchers has identified several proteins as diagnostic biomarkers and potential therapeutic targets for kidney cancer. Subject to follow-up validation testing, inhibition of these proteins and several related pathways holds promise as a form of therapy to slow the growth of kidney tumors.
In a paper published online in the journal Cancer Research, the researchers found high concentrations of specific proteins that point to alterations in three sequences of chemical reactions known as biochemical pathways of mice implanted with human kidney cancer cells. The findings suggest that cancerous tumors modulate the pathways, which in turn makes these pathways potential therapeutic targets.
Nicotinamide and cinnamoylglycine, which were altered as a signature of one of the pathways, are just two of approximately 2,000 chemicals, or metabolites, that the human body produces. Metabolites, referring to any substance produced by metabolism, are a reflection of the body’s processes in real time. The field of study, known as metabolomics, enables researchers to discover biomarkers and to identify novel therapeutic targets.
The study used metabolomics techniques and instrumentation to simultaneously examine chemicals in two biofluids (urine and serum, or blood) as well as tissue from kidney cancer mice models. Seeking to describe the utility of these fluids as tumor indicators, they found that serum metabolomics analysis is the most accurate proxy of chemical changes that are related to kidney cancer.
“It’s exciting to report that our identification of several important metabolic processes may well result in the discovery of diagnostic markers and new therapeutic targets for kidney cancers,” said lead author Robert H. Weiss, a professor in the UC Davis Division of Nephrology, Department of Internal Medicine. Currently, there are no tests to easily identify kidney cancer and current treatments are not always successful, so these markers will be important tools for detection and new treatments of the disease.
For the study, researchers transplanted human kidney cancer cells into a mouse model capable of growing human tumors. Researchers compared the metabolites identified in the implanted mice against those in a control group of mice that had surgery, but no cancer cells implanted.
If further research with mouse models demonstrates that inhibition of the newly identified targets works in therapy, then preparation for human trials will be a next step.
“This research represents collaboration among many kinds of experts, all of whom are concerned that kidney cancer patients have too few treatment options, which often have debilitating side effects,” said Weiss, who serves as chief of nephrology at the Sacramento Veterans’ Administration Medical Center in addition to his work at UC Davis.
The research was funded by the National Institutes of Health and the Medical Service of the U.S. Department of Veterans’ Affairs, grants 1R01CA135401-01A1 and 1R01DK082690-01A1. Other UC Davis authors were Sheila Ganti and Omran Abu Aboud of the Department of Internal Medicine, Sandra L. Taylor and Kyoungmi Kim of the Department of Public Health Sciences, Joy Yang of the Department of Urology, and Christopher Evans of the Comprehensive Cancer Center and Department of Urology. Authors also included Michael V. Osier of the Rochester Institute of Technology and Danny C. Alexander of Metabolon in Durham, N.C.
University of California – Davis Health System