OICR-supported researchers have identified a promising therapeutic target for clear cell renal cell carcinoma.

By blocking the function of a protein that helps kidney cancer grow, OICR-supported researchers may have found a promising new way to slow down the disease.

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer, as well as the deadliest.

But in recent years, researchers like OICR Investigator Dr. Laurie Ailles have found growing evidence of vulnerabilities in how ccRCC cells function that could be exploited with new medications.

In the latest discovery from Ailles’ lab, published in Nature Communications, researchers found that stopping the activity of a protein called PRMT1 stops kidney cancers cells from replicating, and eventually causes them to die.

“Our hope was to identify a new target that could provide a scaffold for drug development for ccRCC,” says Ailles, who is also a Senior Scientist at the Princess Margaret Cancer Centre and an Associate Professor in Medical Biophysics at the University of Toronto.

PRMT1 comes from a family of proteins that regulate important functions in a cell. Based on earlier research, Ailles and colleagues theorized that ‘inhibiting’ these proteins might end up damaging cancer cells.

They tested their theory using a library of compounds that inhibit these types of proteins acquired from the Structural Genomics Consortium, and came away with a promising ‘hit’: PRMT1.

“It looks like there’s a phenotype where, when PRMT1 is inhibited, cancer cells begin to take on a lot of DNA damage, they stop cycling and eventually they die,” says Dr. Joseph Walton, a postdoctoral researcher in Ailles’ lab and the study’s first author.

Their findings about PRMT1 are especially promising for a couple of reasons.

First, the research was done using ‘patient-derived cell lines’ developed by Ailles’ lab. These are research models created from the cells of actual cancer patients, meaning they more accurately reflect human biology. The cell lines Ailles created also have the advantage of being new, compared to models created decades ago, which may have evolved biologically the over the years.

“By using our patient-derived cell lines, we feel that our models are much more representative of what’s actually helping patients,” Ailles says.

It’s also encouraging that therapeutics inhibiting PRMT1 are already in development for other types of cancer, meaning this research has a faster track toward making an impact on patients.

“Hopefully the data from these other studies could help our work translate more quickly to the clinic,” says Walton.

Ailles, Walton and colleagues are now investigating how inhibiting PRMT1 could work in tandem with existing cancer therapeutics that cause DNA damage, like chemotherapy and radiation. They are also exploring other ways to inhibit the PRMT1 ‘pathway’, which could ultimately lead to even better therapeutic candidates that may be safer and more effective for patients.

Ailles says these discoveries wouldn’t have been possible without her OICR Investigator Award.  She says OICR was especially helpful in developing the patient-derived cell lines – the kind of foundational science that drives discovery but can be difficult to get funding for.

“I can’t say enough how instrumental OICR has been in this project, and in so much of my work,” Ailles says.