Canada Research Chair aims to unravel prostate cancer’s defence
April 10, 2025
Fonseca and the Cytokines sounds like 1960s band, but what Nicolette Fonseca is orchestrating is a far cry from a pop song.
Rather, the Canada Research Chair in Systems Approaches to Cancer Biology is integrating cancer genomics with immunology and bridging it all with bioinformatics.
During her PhD, she looked at how the cytokine interleukin-10, a normally occurring anti-inflammatory signalling molecule, drives the balance between protection and pathology during an influenza infection. From there, she explored how this cytokine is regulated, expanding her expertise in bioinformatics, using immunological techniques, DNA sequencing and computation to capture and interpret immune cell behaviour.
Her research took a pivotal turn after meeting with a cancer genomics expert who later became her postdoctoral mentor. “Learning that advanced prostate cancer is largely resistant to immunotherapy fascinated me, and I immediately wanted to understand why,” she recalls. Since tumours arise from genetic changes that disrupt normal cell function, her postdoctoral work focused on identifying genetic alterations that drive prostate cancer and have the potential to modulate immunotherapy response.
To create a genetic profile of a patient’s cancer, she uses a minimally invasive test that detects tumour-derived DNA fragments, called circulating tumour DNA, in blood. In a recent publication, she demonstrated that the abundance of circulating tumour DNA in a patient’s blood can inform on prostate cancer aggression and response to standard treatments.
Now, as a new faculty member in UVic’s Department of Biochemistry and Microbiology, Fonseca is investigating how certain aggressive types of prostate cancer interact with — and evade — the body’s natural immune responses, allowing the cancer to spread. Once prostate cancer metastasizes, she explains, it is not curable and is one of the leading causes of cancer-related death among Canadian men. With that in mind, her work takes on an urgent tempo.
“My goal is to design new immune-based therapies that can overcome prostate cancer’s immune resistance and ignite a robust anti-tumour immune response,” she says. “But there’s always a balance - you need enough immune activity to eradicate the cancer, while minimizing the risk of adverse immune-mediated side effects.”
First, she’ll develop a blood test that will track the timing and type of certain genetic alterations that enable tumour cells to hide from the body’s natural immune responses.
By identifying features within the tumour cells and in the environment around them, she plans to develop methods for predicting whether a particular type of tumour will respond to treatment — and, indeed, which treatment.
“We’re likely going to need a combination of therapies,” she says.
And she’s using a suite of technologies and resources to get there. With her Canada Research Chair, she received funding from the Canada Foundation for Innovation’s John R. Evans Leaders Fund for state-of-the-art research equipment. With this, she’ll conduct spatial transcriptomics to map gene activity in intact tumour tissue, analyse circulating DNA from blood and access high-performance computing to view and analyze data from these human samples.
Collaboration is key. Fonseca will work with colleagues at UVic, the Deeley Research Centre and BC Cancer to translate her laboratory findings to the clinical setting.
“By leveraging this highly collaborative environment, I want to transform what I learn,” she says, “to develop immuno-genomic guided treatments, and bring them to the clinic to ultimately benefit patients.”
Rachel Goldsworthy