The National Cancer Institute has awarded UC Davis researchers $1.25 million to fund a five-year project focused on identifying diagnostic biomarkers for kidney cancer. The grant will enable research that sets the groundwork for developing a new, simple test to detect kidney cancer in its early stages when it is most treatable.
Although kidney cancer accounts for just fewer than 2 percent of all cancers globally, the incidence of the disease is rising.
The five-year patient survival rate drops from 95 percent to about 5 percent if kidney cancer is diagnosed after it has metastasized to distant organs. However, there are no screening tests currently available for early detection of the disease, which is the sixth leading cause of cancer death in the U.S.
Many patients are diagnosed incidentally during screening for other kidney problems, according to Robert Weiss, a professor of nephrology at UC Davis and principal investigator for the grant.
Weiss will team up with other researchers who believe that kidney cancers produce a distinct chemical profile of metabolites – byproducts of metabolism – that can be picked out in patients‘ urine.
“We’re taking a different approach where instead of looking at genes, we’re looking at pathways that are altered [in cancer],” Weiss said.
Tumors are known to have revved up metabolisms compared to slower-growing normal tissue. The researchers speculate that, in the case of kidney cancer, cellular processes contributing to fast tumor growth will overproduce certain metabolites that show up in urine. They suspect that characteristic chemical profiles may also reflect specific mutations that give rise to the cancer.
“Kidneys are known to have active roles in body metabolism, and its excretions are readily discernible in urine,” said Oliver Fiehn, an associate professor at the UC Davis Genome Center who is advising Weiss for the project. “That’s why [kidney cancer] might be a good target for finding metabolic markers.”
The proposed study is by no means a trivial task. Urine contains thousands of metabolites, and identifying them can be technically challenging, Weiss said.
The researchers will also need to control for many factors that can affect the metabolic profile of urine samples collected from the 50 patients they plan to enroll for the study.
“If you’re looking for a specific test for [kidney] cancer, you have to control for people with kidney failure or people with some other kind of cancer because we don’t want to test for all cancers,” Weiss said.
The researchers will use chemical analysis methods to detect potential biomarkers as differences in the metabolic profiles – what they call “blips” – between patients with and without kidney cancer. Once they identify candidate metabolites in urine, the researchers will then perform a blind study with another group of patients for which kidney cancer status is unknown. The goal will be to confirm that proposed biomarkers are useful for identifying who does or does not have kidney cancer in an unbiased manner.
“We’re looking for profiles that are characteristic of kidney cancer in the stage that it’s [diagnosed], and so extrapolating backwards, we’re hoping that we’ll see [those profiles] to maybe a lesser extent [in the earlier stage],” Weiss said.
Another major goal of the project is to find markers of kidney cancer that will quickly indicate if a particular therapy is working or not.
“At a more fundamental level, biomarkers of kidney cancer may lead to mechanistic understanding that could in turn lead to new therapies or better support for patients undergoing therapy,” said Bruce Hammock, a UC Davis professor of entomology who is also on the research team.
The researchers hope that results gleaned from the project will eventually translate into a reliable urine test that doctors can conduct during routine examinations to screen for kidney cancer.
ELAINE HSIA can be reached at features@theaggie.org.
