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Liquid Biopsies: A Potential Game-Changer In The Fight Against Cancer?

May 6, 2019

While new treatments are being developed to defeat cancer, the key to a favorable cancer prognosis is still early detection.1 Although early detection doesn’t guarantee that a cancer can be treated,2 it is important because the longer a tumor grows, the more mutations it accumulates, the more heterogenous the cells composing it, and the more resistant it is to treatment.3,4

 

The current gold standard for cancer detection is a tissue biopsy, during which a tissue sample is taken from a living subject for examination.5 However, this is a costly, time-intensive, invasive procedure that can cause the patient pain.6 Another downside is that obtained tissue biopsy samples may not be sufficiently large, and only represent a local sample – meaning that the genetic profile of any obtained tumor cells is a spatially and temporally limited snapshot.3 Since tumors, especially at later stages, are highly heterogeneous and evolve quickly, clinical decisions based on these biopsies can be underinformed.3

 

Liquid biopsies may overcome these hurdles.6 A liquid biopsy is a test done on a biofluid sample – usually blood, although this has since branched out to also include urine, saliva, and cerebrospinal fluid - which looks for circulating tumor cells (CTCs) and cell-free nucleic acids (typically circulating tumor DNA, or ctDNA).7,8 ctDNAs are tiny DNA fragments that enter the blood stream as cancer cells die (within a tumor, cells are constantly multiplying and dying), and their levels increase with tumor stage.6,8

 

A blood sample liquid biopsy is easy to obtain. It is quick and causes minimal pain to the patient. Unlike a tissue biopsy, it is not a localized sampling, and instead allows doctors to see the evolution of the genetic landscape – including both genetic and epigenetic changes – of both primary and metastatic masses in the body over time.9

 

What information can be gleaned from these liquid biopsies? Liquid biopsies might be able to detect early cancer in asymptomatic individuals, predict relapse, measure tumor size, determine prognosis, and monitor treatment.10

 

 Intact CTC levels in the blood can give a prognosis for overall survival.8 The collection of these cells has been challenging until recently, when isolation of live cells has become possible due to the development of new techniques.11 These cells can provide information at the DNA, RNA, and protein levels.8

 

ctDNA might provide even more insights. Cancer is associated with genetic mutations, including chromosomal rearrangement, point mutations, and hypermethylation,5 and the DNA fragments that tumors shed into the bloodstream can provide temporal information about molecular changes in real time.9 Polymerase chain reaction-based sequencing techniques can allow us to measure levels of ctDNA with specific kinds of mutations.12 Especially exciting is the fact that many patients without detectable CTCs still have detectable ctDNA.13

 

Apart from potential for earlier detection of cancer, liquid biopsies can also assist doctors in treating patients already diagnosed with cancer. Liquid biopsies can allow doctors to tailor and individualize treatments for specific patients,14,15 working in conjunction with other relatively new cancer-treating strategies, such as immunotherapy, in which the body’s immune system is leveraged against the cancer.16 By providing doctors with the ability to track molecular changes over time in the tumor, liquid biopsies can allow the effective planning of treatments for specific patients.9

 

Liquid biopsies can also monitor patients’ responses to treatment. Successful treatment causes ctDNA levels to decrease, since ctDNA levels are correlated with tumor size.8 A smaller tumor has fewer apoptotic and necrotic cells and therefore releases less ctDNA.8 Furthermore, increases in ctDNA can be observed months before the recurrence of cancer is detectable via other methods.17

 

While liquid biopsies are an exciting new tool in the fight against cancer, they are still a long way from becoming a standard part of cancer-detection protocol. Liquid biopsies still have many shortcomings.  Most importantly, the validity of liquid biopsy diagnosis is still being investigated.7 High reliability for a cancer-detecting test is critical because, apart from being dire news for patients, false positive test results could result in undue invasive and expensive tests.10 One potential issue for example, is that ctDNA levels increase with age even for people who do not develop cancer during their lifespan.18 In addition, researchers don’t yet know how accurate the test is for different tumor types and stages of disease and it is still unclear whether a liquid biopsy can predict how aggressive a cancer could be.13,2 Additionally, liquid biopsies are still prohibitively expensive for routine use, requiring labor, equipment, and expensive reagents.5

 

The most immediate application of the liquid biopsy is the testing of the evolution of the genomic landscape in already diagnosed cancer patients and their reaction to treatments.2 Currently, liquid biopsies are only being employed for research purposes or to evaluate the effectiveness of treatments.5 They are becoming a part of clinical practice in oncology departments treating breast, ovarian, cervical, lung, melanoma, and bladder cancer. improving prognostic and preventative procedures.19

 

As far as the early diagnosis of cancer goes, for the foreseeable future liquid biopsies are likely to primarily be a compliment to tissue biopsies, allowing the testing of more patients.7 With more research, perhaps physicians, biochemists, and bioinformatics specialists m ay advance them so they will become a more central tool for cancer diagnosis.5

 

Viola Schmid is the creator of Neural Academy, a YouTube channel focused on biology education. She graduated from the University of Toronto with a BSc in Neuroscience and Geoscience.

 

 

Opinions are solely of the author and not Boustead & Company Limited and its affiliates.

 

Sources:

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881453/

  2. https://www.cancer.org/latest-news/liquid-biopsies-past-present-future.html

  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009092/

  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC298677/

  5. https://bmccancer.biomedcentral.com/articles/10.1186/s12885-018-4433-3

  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356857/

  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881079/

  8. https://www.sciencedirect.com/science/article/pii/S1535610817300028

  9. https://www.ncbi.nlm.nih.gov/pubmed/23836314

  10. https://www.ncbi.nlm.nih.gov/pubmed/30285732

  11. https://www.ncbi.nlm.nih.gov/pubmed/26484313

  12. https://www.ncbi.nlm.nih.gov/pubmed/27060140

  13. https://www.hopkinsmedicine.org/news/media/releases/dna_shed_by_tumors_show_promise_for_non_invasive_screening_and_prognosis

  14. http://tcr.amegroups.com/article/view/4546

  15. https://www.ncbi.nlm.nih.gov/pubmed/26307395

  16. https://www.ncbi.nlm.nih.gov/pubmed/29601334

  17. https://books.google.ca/books?id=NKCpDQAAQBAJ&pg=PT86&lpg=PT86&dq=ctDNA+observed+months+before&source=bl&ots=rwo_L5dFF1&sig=ACfU3U3-2lMRvQG1JpVkb4ESKQMT8n4gZg&hl=en&sa=X&ved=2ahUKEwj3wtLJsuzgAhUn4IMKHexPAYcQ6AEwBXoECAMQAQ#v=onepage&q=ctDNA%20observed%20months%20before&f=false

  18. https://www.nejm.org/doi/full/10.1056/nejmoa1409405

  19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5179978/

     

     

     

     

     

     

     

     

     

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