Cancer physicians at Indiana University and scientists at Purdue University are working to develop a urine test that would enable patients to avoid an invasive, painful biopsy to detect a type of kidney cancer.
Ronald S. Boris, MD, a physician with the Indiana University Melvin and Bren Simon Comprehensive Cancer Center, treats people with various types of renal cell carcinoma, which are kidney tumors and cancers. During a two-year stint at the National Institutes of Health, he focused on hereditary kidney cancer.
Boris, who specializes in urologic oncology surgery, wondered if a simple test—such as a urine test—could be developed that would help him and other physicians create personalized treatment plans for patients with renal tumors.
“Could we create a test, whether it would be a urine-based test or a serum-based test, to characterize renal tumors in patients who have an isolated renal mass?” he wondered. “Instead of doing a biopsy, could we have a patient come into the office with a urine specimen, test the specimen to determine whether it’s a clear cell cancer, a papillary tumor, a low-risk tumor or a high-risk tumor that would spread in five years or 10 years?”
Such a test would enable physicians to offer unique treatment plans for individual patients. It’s something that’s already done for patients with prostate cancer. Why couldn’t it be done for kidney cancer?
Boris’ question could best be answered by a basic scientist, someone who devotes his or her time in a research laboratory.
His quest led him to W. Andy Tao, PhD, of the Purdue Center for Cancer Research. Tao, a biochemistry professor in the Purdue College of Agriculture, previously discovered a method to detect and monitor breast cancer using a simple blood test and bladder cancer using a urine test.
Tao suggested that analyzing the proteome, or group of proteins, in urine extracellular vesicles (EVs) might help them to classify renal tumors by their aggressiveness and subtypes. Analyzing proteomes can help researchers identify cancer biomarkers.
According to Tao, “EVs are particles naturally secreted from all types of cells. They carry important markers of the cell-like proteins, DNA and RNA cargo, and lipids, and have functions that include intercellular communication which contribute to the pathogenesis of several diseases. I like to call them the ‘Ubers’ of the cell, which transport relevant targets into other cells, and therefore, influence processes in the recipient cell.”
They tested the idea thanks to a $40,000 grant from Indianapolis-based Walther Cancer Foundation Inc. as part of the Walther Embedding Program. The preliminary funding led them to study about 10 tumors with different renal subtypes. Boris, associate professor of clinical urology at IU School of Medicine, said by testing and applying the EV pipeline to isolate and analyze the proteins from the vesicles in human urine, they were able to identify the subtypes of renal cell carcinoma.
Using tumor tissue data from the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC), the group demonstrated significant overlap with the proteins and phosphoproteins isolated from urine EVs study tumors, suggesting that EVs may represent useful targets to develop a urine-based test for renal cell carcinoma.
After earning a second Walther grant of $200,000, the group has been conducting experiments to test their theory using much larger sample sizes across the multiple renal tumor subtypes.
“The Walther Cancer Foundation is pleased to see the successful collaboration between physicians and scientists at IU and Purdue as a part of the Walther Cancer Foundation Embedding Program,” Thomas W. Grein, president and CEO of the Walther Cancer Foundation, said. “The complementary talents of Drs. Boris and Tao are combining to improve patient outcomes. This is the primary goal of the program.”
Boris plans to apply for additional grants to continue this study with the goal of offering patients more effective diagnostic testing instead of invasive biopsies and CAT scans that are currently offered. The current diagnostic tests are typically done only after a person is experiencing symptoms, a sign that the disease has already progressed. Down the road, the IU-Purdue work might lead to improved detection, diagnosis and treatment.
IU’s Boris goes to Purdue, Purdue scientists go to IU
The duo didn’t reach their findings while working separately. Boris spent time in the Tao lab, gaining hands-on experience studying proteins. Meanwhile, graduate students in Tao’s lab at Purdue—Hillary Andaluz Aguiliar and Marco Hadisurya–traveled to IU in Indianapolis to spend time in the operating room with Boris. While there, the students gained experience using the robotic surgical equipment that Boris specializes in.
In addition, the students followed Roberto Pili, MD—a nationally recognized expert in prostate, renal and bladder cancers—in his clinic at IU, offering real-world interactions with patients. Pili, who is now at the University of Buffalo, was the IU principal investigator of this study.
“This embedding project creates an environment in which scientists collide with clinicians, leading to an environment in which both groups think how they can best work for the benefit of the patient,” Boris said. “Ultimately, if we can characterize the tumor, its subtype and its metastatic risk, we can then integrate that knowledge into a care plan for the patient. That’s a personalized plan for the patient, which is well beyond what we can offer now.”
About the Walther Embedding Program
The Walther Cancer Foundation Embedding Program’s goal is to cross-train a cadre of young Indiana University and Purdue University clinicians, physical and computer scientists, and engineers. The program’s focus is on exposing junior clinical and physical scientists and engineers to each other's culture. The goal is to impact their future approach to translational science and improve patient care.