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Physician Information

A malignant tumor is a bustling metropolis populated by many different kinds of cancer cells, where each one is different from the rest and can act differently within the same tumor.   


The two blood tests CA 15.3 and CEA have been in clinical use for decades to monitor breast cancer and colorectal cancer recurrence respectively. Both tests are known to be severely limited in their effectiveness. They only apply to 25% of the disease population and recognize patients mostly in the  later stages of disease.


Recent liquid biopsy tests are based on tiny circulating tumor DNA (ctDNA) fragments in the blood. These tests suffer from a lack of sensitivity, specificity and other technical issues. Abundant literature from the public domain that highlights the clinical limitations in the utility of ctDNA. Some limitations include: 


  • Huge amounts of circulating DNA ,unrelated to cancer, are released into the bloodstream everyday as cells in our body naturally become old and die as part of the natural cellular renewals and aging process.
  • Healthy individuals can release in their blood, mutated DNA as a result of environmental exposure (pollution, toxic materials, foods, etc...). So mutated circulating DNA fragments in the blood are not necessarily cancer-related.
  • Cells isolated from the same biopsy of the same patient or found in their blood differ substantially from one another genetically (1,2).
  • Mutations are also found in bone marrow progenitor cells and hematopoietic cells that are unrelated to cancer mutation but can complicate further the interpretation of mutations found in circulating DNA in the blood (3,4).


Recommending therapeutic interventions to cancer patients, based on the genetics of heterogeneous cancer cells that change constantly begs the question of the real clinical value of ctDNA!

Art Courtesy of Michael Murphy

Citations

(1)https://med.stanford.edu/news/all-news/2012/05/not-all-tumor-cells-are-equal-study-reveals-genetic-diversity-in-cells-shed-by-tumors

(2)https://www.cell.com/action/showPdf?pii=S0092-8674%2821%2900294-4 

(3)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245510/pdf/atm-02-11-107.pdf

(4)https://aacrjournals.org/clincancerres/article/24/18/4437/80899/False-Positive-Plasma-Genotyping-Due-to-Clonal

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