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.


References

  1. https://cancer.ca/en/research/cancer-statistics/cancer-statistics-at-a-glance
  2. https://cancer.ca/en/about-us/media-releases/2021/canadian-cancer-statistics-report-2021(Canadian Cancer SocietyStatistics)
  3. https://www.cancer.org/treatment/understanding-your-diagnosis/tests/testing-biopsy-and-cytology-specimens-for-cancer/cytology-types.html (American cancer society)
  4. https://www.cancer.gov/news-events/cancer-currents-blog/2017/liquid-biopsy-detects-treats-cancer (NIH Blog)
  5. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/liquid-biopsy (Definition of liquid biopsy)
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009092/#r5 (Pros: Can tissue biopsy be replaced by liquid biopsy?)
  7. https://www.nature.com/articles/nrclinonc.2013.110 (Liquid biopsy: monitoring cancer-genetics in the blood)
  8. https://pubmed.ncbi.nlm.nih.gov/30796368/ (Liquid biopsy and minimal residual disease –latest advances and implications for a cure)
  9. https://www.galleri.com8.https://grail.com/our-approach/ (company website)
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Daniel Zangrando

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