Implementing a pan-Canadian standardized mass spectrometry-based proteomics approach for the analysis of clinical cancer samples: validation using archived breast cancer specimens for biomarker discovery

Using a standardized approach to map proteins to search for new therapeutic targets  

If your body were a factory line, DNA would be the blueprint, containing all the instructions needed to build and maintain it. Downstream you would find RNA, which acts as the factory supervisor, taking instructions from DNA and guiding the production process. Finally, you get to the workers – proteins – which actually build structures and perform specific tasks based on the instructions they receive.

Current precision oncology approaches mostly profile the two upstream players – DNA and RNA – in search of alterations that can be targeted through new or existing therapies. Yet, while these therapies are chosen based on changes to DNA and RNA, they usually actually work by disrupting the function of proteins, which are, after all, the primary agents of disease.

In this context, being able to map the proteins that cause cancer in each individual and find ways to target them more specifically emerges as a promising way to personalize cancer treatments. However, a lack of standardized methods to profile the proteome has limited our ability to effectively do so.

That is why a team of pan-Canadian researchers will use new funding from the Terry Fox Research Institute and the Marathon of Hope Cancer Centres Network to develop a standardized approach that uses mass spectrometry to measure thousands of proteins in individual patient samples, getting us one step closer to being able to target them for precision oncology treatments.

“Our goal through this project is to demonstrate a standardized approach that can be used to examine tumour tissue samples to identify variation in protein amounts between individual cancer patients,” says Dr. Paola Marcato, a professor at Dalhousie University in Halifax, who will co-lead the team with Drs. Karama Asleh and Christopher Hughes (Dalhousie University) and Dr. Gregg Morin (BC Cancer). “This will help advance precision medicine for cancer by enabling the development of personalized treatment plans tailored to individual patients' unique protein profiles, meaning that patients can receive the most effective treatment for their specific type of cancer, reducing trial and error and improving outcomes.”

The team will test this method's reproducibility, repeatability, and scalability to ensure consistent results across multiple laboratories and institutions, which will facilitate widespread adoption of this protein detection technology across the Marathon of Hope Cancer Centres Network. This will allow them to pilot the incorporation of proteomic analysis to the Network’s Gold Cohort, which already includes DNA, RNA, and clinical data from thousands of cancer patients treated in centres across Canada.

“By creating and validating this approach, we aim to enable researchers nationwide to confidently acquire protein profiles from cancer patient tumours and compare them to DNA, RNA, and clinical data to find better ways to personalize therapies,” explains Dr. Marcato. “We are setting the stage for a future where protein profiles are as widely used and trusted as genetic data in the fight against cancer.”