Cancer is the leading cause of death in Canada and requires an early diagnosis to improve patient outcomes. It is estimated that in 2021, approximately 239,000 Canadians are anticipated to have a cancer diagnosis, with lung, colorectal, breast, and prostate cancer being the most frequent. While clinical symptoms or the unexpected detection of a tissue mass can initially signal that cancer may be present, a tissue biopsy remains the fundamental diagnostic test required to correctly identify cancer. Doctors examine the suspected tissue and screen for abnormal morphology along with cancer biomarkers to make a formal diagnosis and construct a treatment plan.
However, a tissue biopsy is an invasive procedure that cannot be regularly repeated, especially if the tumour is in a remote or sensitive location, which hinders a doctor’s ability to monitor a patient’s cancer progression. Additionally, cancerous tumours are heterogeneous. As such, biopsied tissue samples only represent a small section of the tumour tissue and might not capture the presence of treatment-resistant subpopulations of cells. A liquid biopsy, the examination of cancer cells and tumour-released genetic material in the bloodstream, is emerging as a potential non-invasive alternative to a tissue biopsy and is the forefront in cancer diagnostics research.
Cell-free DNA (cfDNA) is one of the main liquid biopsy biomarkers of interest. cfDNA refers to small fragments of DNA, around 200 base pairs in length, that are released into the bloodstream and are suspected to primarily originate from cell death and secretion. cfDNA from cancer cells contain certain genetic mutations and gene expression modification patterns (e.g., methylation) that differentiates them from cfDNA originating from other cells. Cancer patients have greater levels of cfDNA circulating in the blood, however, typically most of their cfDNA will still originate from non-cancerous sources which has previously made it challenging to develop a cfDNA cancer diagnostic test. Circulating tumour cells (CTCs) can be used as a joint biomarker in liquid biopsy analysis. CTCs may have an abnormal expression of cell surface proteins and/or have an enlarged cell size. These characteristics can be used to help differentiate CTCs from other cells in the blood. The purpose of CTC diagnostic test development is to utilize CTCs as a potential biomarker to predict metastatic relapse in cancer patients in remission.
A novel liquid biopsy test that employs cfDNA has been developed by GRAIL, a biotechnology company established in 2015. The test, named Galleri, sequences patient cfDNA and screens for methylation patterns. The Galleri test utilizes computer algorithms to analyze the cfDNA by flagging patient methylation patterns that are characteristic of that in many types of cancer. The Galleri test aims to function as an early cancer detection tool in asymptomatic adults who have a higher risk of developing cancer, particularly those 50 and older. Previous clinical studies suggest that Galleri can be used to detect over 50 types of cancer from one vial of blood potentially revolutionizing cancer diagnostics. However, the Galleri test doesn’t claim to be a replacement for traditional diagnostic tests and warns that it should only be used in combination with other screens. Although the price may vary by healthcare provider, the Galleri test is listed at a costly $949 USD, which may discourage many asymptomatic adults from purchasing the test.
It remains uncertain as to whether liquid biopsy tests will become the primary screen used to diagnose cancer. However, there are many apparent advantages to using liquid biopsy tests to monitor tumour progress and cancer remission. For example, single liquid biopsy samples can represent the biomarkers found in both the primary tumour as well as any metastatic sources. Ultimately, liquid biopsies are rapid, non-invasive, and have the potential to provide flexible, routine cancer surveillance.
- https://cancer.ca/en/about-us/media-releases/2021/canadian-cancer-statistics-report-2021(Canadian Cancer SocietyStatistics)
- https://www.cancer.org/treatment/understanding-your-diagnosis/tests/testing-biopsy-and-cytology-specimens-for-cancer/cytology-types.html (American cancer society)
- https://www.cancer.gov/news-events/cancer-currents-blog/2017/liquid-biopsy-detects-treats-cancer (NIH Blog)
- https://www.cancer.gov/publications/dictionaries/cancer-terms/def/liquid-biopsy (Definition of liquid biopsy)
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009092/#r5 (Pros: Can tissue biopsy be replaced by liquid biopsy?)
- https://www.nature.com/articles/nrclinonc.2013.110 (Liquid biopsy: monitoring cancer-genetics in the blood)
- https://pubmed.ncbi.nlm.nih.gov/30796368/ (Liquid biopsy and minimal residual disease –latest advances and implications for a cure)
- https://www.galleri.com8.https://grail.com/our-approach/ (company website)