The Canadian Cancer Clinical Trials Network (3CTN) is pleased to announce, in collaboration with Janssen Canada, funding of $500,000 to a study led by Dr. Kim Chi of the Vancouver Prostate Centre and the BC Cancer Agency. The study will evaluate the use of cell-free (or cfDNA) profiling to identify genomic alterations in patients with castration-resistant prostate cancer (CRPC), the lethal form of prostate cancer that has become resistant to hormone treatments.

Researchers on Dr. Chi’s team will use the information they discover from cfDNA profiling to match patients with more targeted, personalized treatment. The study will establish the first umbrella trial for CRPC patients and could potentially identify new treatments and predictive biomarkers for the disease.

We spoke with Dr. Chi to explain the work and the challenges his team plan to address in bringing his research to the clinic.

What is cfDNA and why it is useful in predicting response to treatment?

cfDNA is “naked” DNA floating in the blood stream. In patients, it consists of both normal DNA as well as cancer DNA. The cfDNA can be isolated from plasma and then profiled – in this case using gene sequencing techniques – to look for gene mutations and copy number changes. In this way, we can do a type of “liquid biopsy” on cancer.

Why did you and your collaborators choose to approach the problem of metastatic CRPC, as you do in this trial?

Prostate cancer is difficult to molecularly characterize since the original disease typically does not reflect the later stages of lethal prostate cancer and because prostate cancer mainly metastasizes to bone, which is difficult to biopsy both for the patient and the doctor to obtain sufficient tissues to analyze. The treatments for prostate cancer beyond hormone therapy are also not specific – we do not yet have particular molecular markers to tell us which specific targeted treatments to give individual patients. So there is a big need for a liquid biopsy approach for patients with prostate cancer, such as with our techniques to analyze cfDNA, so that we can develop prognostic and predictive markers to help us decide which treatments to give to whom.

Personalized medicine is still a relatively new concept. Can you please explain the importance of trials such as yours and any unique challenges you face?

Over the past decade, prostate cancer therapies have become increasingly personalized to individual patients. Personalized or precision medicine is important because we know that on a genomic level, CRPC is made up of a diverse population of cancers. As the targeted therapies used in precision medicine only act on a specific genetic mutation in that individual’s cancer, it is important to test any potential targeted therapies in the patients who have that specific mutation in their cancer. If we were to test a targeted therapy without prequalifying patients, then only a minority of patients would possibly respond and the drug may be incorrectly categorized as ineffective.

In our trial, by using the cfDNA analysis we will identify patients that are more likely to respond to a targeted treatment. The challenge is that cancer biology is very complicated, there are multiple layers of redundancy and interconnected pathways and unfortunately just because something should work, doesn’t mean that it will. However, we have to start somewhere, and even a small step forward will be huge progress for patients with CRPC.

How will the infrastructure and resources of 3CTN assist you in conducting this clinical trial?

The funds 3CTN has provided will enable this study to proceed. The 3CTN network will also help to raise awareness of the trial, which is important because it will be conducted at multiple cancer centres.