Study Targets Aggressive Form of Kidney Cancer

By Dirk Hoffman

Pili, a professor in the Department of Medicine and chief of the Division of Hematology/Oncology, is leading the study titled “Therapeutic Targeting for Translocation Renal Cell Carcinoma.”

“We are trying to learn more about the biology of this relatively rare tumor called translocation renal cell carcinoma (tRCC) found primarily in children or young adults,” Pili says. “This type of tumor is aggressive, and the standard therapies utilized for the most common types of kidney cancer do not work.”

Over the years, several studies have identified a specific alteration in the genome of these tumors.

Pili says DNA undergoes a “cut and paste” phenomenon that leads to the expression of malignant proteins called TFE3-Os.

Pili’s lab has recently established the growth of one of these tumors in mice and determined that the malignant proteins are responsible for the aggressive behavior of these cancers.

To better understand the disease, the new study builds upon earlier research that used models from patients with kidney cancer that have TFE3-SF gene fusions.

TFE3-splicing factor fusions are proteins that affect both gene expression and the splicing of RNA. These fusions change how genes are read and how RNA is processed.

By activating specific inhibitors that block their ability to pair up, Pili says researchers can slow down the growth of kidney cancer caused by these fusions.

“We recently published several potential candidates for therapies — one is an antihistamine commonly used for allergies with the brand name Allegra, which is no longer on the market,” Pili says.

The new grant will allow Pili’s lab to collaborate with David E. Heppner, PhD, Jere Solo Assistant Professor of Medicinal Chemistry in the Department of Chemistry in UB’s College of Arts and Sciences, to further understand how the malignant proteins work in tRCC.

“We are going to try and modify this antihistamine drug to make it more potent and less toxic,” Pili says. “We will combine this therapy with existing therapies. I believe we will eventually be able to utilize this same drug for this rare type cancer also on more common types of kidney cancer as well.”

Pili says the alliance with Heppner, who also holds an appointment in the Department of Structural Biology in the Jacobs School, makes for an “exciting project that is an example of the great collaborations the UB Cancer Research Consortium has been able to foster.”

“It allows us to pool people together who are experts in different fields to work together toward a common goal.”

Pili says his lab is among a handful group of labs working on new therapeutic strategies for tRCC.

“Like any orphan disease, there is not as much commercial interest. The pharmaceutical companies want to address diseases that affect the most people,” he says. “Not unlike any other orphan disease, tRCC does not have as much research and commercial support.”

“But besides the value of the research we are doing, it is really a great example of the types of collaboration that we are establishing at UB across the different schools and across the different campuses,” Pili added.

Jeffrey C. Miecznikowski, PhD, associate professor of biostatistics in UB’s School of Public Health and Health Professions, is also a co-investigator on the grant. He holds a secondary appointment in the Department of Orthopaedics at the Jacobs School.