A pioneering approach is offering researchers new insights into why some prostate cancers are more aggressive and difficult to treat.
In a new application to prostate cancer research, Vancouver Coastal Health Research Institute scientists have used a sequencing technique – called plasma cell-free chromatin immunoprecipitation sequencing (cfChIP-seq) – on blood samples from patients with advanced disease, revealing biological factors that may drive disease progression.
This work, funded in part by a Terry Fox New Frontiers Program Project Grant that includes Dr. Alexander Wyatt, is an important step toward understanding the epigenomic makeup of prostate cancer and identifying targets for personalized treatment.
“From a simple blood sample, we demonstrated that cfChIP-seq captures clear patient-to-patient variations in the epigenomes of their prostate cancers, partly explaining the divergent clinical characteristics of each patient’s disease,” states Dr. Wyatt, an associate professor in the Department of Urologic Sciences at the University of British Columbia (UBC).
“Understanding the biological determinants of different clinical patterns is a key step towards optimizing cancer care based on each patient’s individual needs.”
A new way to understand prostate cancer
Unlike traditional methods, which require an invasive tissue or bone biopsy of a cancerous region to study a tumour, cfChIP-seq offers a non-invasive way to examine small fragments of tumour DNA – known as circulating tumour DNA (ctDNA) – from a standard blood draw.
“This research tool opens up a new dimension of biology for us to study. Prior technology enabled us to know whether a gene had been mutated or not. However, the fact that cfChIP-seq can tell us whether a gene is turned on or off gives us greater granularity,” says Dr. Cameron Herberts, a postdoctoral fellow at the Alex Wyatt Laboratory.
“We know that patients whose prostate cancer has spread to the liver can have different presentations and typically worse outcomes than individuals whose prostate cancer spreads only to their bones. These tumours can be very aggressive and difficult to treat,” says Dr. Herberts.
“Being able to anticipate the metastatic trajectory of a prostate cancer earlier on in the disease progression would lead to better-informed treatments tailored to a patient’s specific disease biology.”
Researchers also found that some of the information from the cfChIP-seq profile of a patient with metastatic prostate cancer could be mapped to the other organs affected by their cancer, rather than originating from the tumour itself.
“This suggests a potential role for cfChIP-seq in forecasting cancer-related organ damage before symptoms arise or monitoring recovery in real-time during treatment,” says Dr. Herberts.
Further research is needed, but cfChIP-seq shows promise as a tool for tracking cancer’s impact on the body.
Unpacking the epigenetic code of prostate cancer
By measuring specific molecular tags on nucleosomes, which help regulate how genetic information is packaged and which genes are active, researchers are able to learn which genes are turned on or off.
According to Dr. Wyatt, understanding how genetic information is packaged in cancer cells is critical for understanding its behaviour and clinical outcomes, and in matching patients to the best therapy for their mutations.
“Understanding not only how the genetic code of prostate cancer subtypes differs, but also how the genes are organized and packaged, is taking us to the next level of cell regulation research in prostate cancer,” says Dr. Wyatt.
“This new dimension of functional biology could help researchers understand how genes are working in relation to disease, potentially identifying new biomarkers of disease down the road,” says Dr. Herberts.
Moving forward, Wyatt and Herberts are exploring broader clinical uses of cfChIP-seq, including its potential to benefit patients with other cancers.
A version of this story was originally shared by the Vancouver Coastal Health Research Institute.