A group of researchers
at the John Hopkins School of Medicine discuss the current status of advances
in liquid biopsies and the applications in cancer detection and monitoring.
‘Liquid biopsies enable close monitoring of cancers in a minimally non-invasive method. Also, liquid biopsies have the potential to detect, characterize, and monitor cancers much earlier than conventional methods.’
The search for
minimally invasive methods to detect and monitor cancers has been on for quite
some time. The last ten years have seen tumor-derived material in various
biofluids like saliva, urine and cerebrospinal fluid. There have been numerous
advances in the development of sensitive assays to detect cancer-specific
analytes in biofluids.
What are the Types of
In liquid biopsies,
the analytes used include circulating tumor cells (CTCs),
cell-free tumor DNA (CtDNA), proteins, metabolites, mRNA, miRNA and exosomes.
While CTCs are rare in early cancers, a good quantity can be found in
When cancers release
DNA into body fluids, they can be detected with high precision digital
technologies like massively parallel sequencing where each DNA is analyzed
separately. In normal individuals with early-stage cancer, almost 3-9 ng of
cell-free tumor DNA
(ctDNA) is found per milliliter of plasma.
cancers, this can
go up by tenfold in the amount of ctDNA per milliliter of plasma. To be able to
robustly detect and monitor cancers multi-analyte
evaluations of DNA, proteins, metabolites and RNA are required. There are many
challenges regarding developing a single test using several platforms and at
the same time maintaining sensitivity and cost-effectiveness.
Role of Liquid
Biopsies in Detecting Cancer
The paper discusses
the use of analytes and liquid biopsies in four clinical scenarios of cancer:
Precision medicine relies on the premise of identifying cancer
mutations at the earliest for patients to access the right therapies.
Liquid biopsies are less preferable at this stage as the biopsy from the
primary tumor will enable clearer identification of biomarkers and mutations.
At this stage, liquid biopsies may be more suitable for prognosis. Liquid
biopsies are more suitable for unresectable cancers with insufficient tissue
from aspirate for DNA sequencing The only DNA available here would
be through a non-invasive liquid biopsy.
2. After surgery – This method at this stage is
very promising for prognostication. Patients with circulating ctDNA or CTCs
after surgery are most likely to have a relapse. Patients without ctDNA are
less likely to have relapsed cancer. If the liquid biopsy detects positive
ctDNAs in a patient, adjuvant therapies can be planned at this stage. Even
those patients who present without ctDNA need careful monitoring as occult
disease sensitivity is not 100%.
3. After additional
Liquid biopsies are rightly positioned to detect early recurrences of the tumor
even before it becomes apparent in radiographic or other clinical evaluations.
If a patient presents with a relapse, liquid biopsies can reveal new mutations
which may not even be present in the primary tumor. Such an evaluation can
guide second-line treatment and therapies.
4. Cancer screening – This is the most valuable and
most difficult of all applications of liquid biopsies. While the above three
applications are at the diagnostic stage, this application is at the screening
stage itself to preempt cancers. This can have a huge impact by reducing
morbidity and mortality due to cancers.
The next decade for
liquid biopsies should see robust applications in the screening stage. It
should be able to detect cancers earlier than it would normally be detected for
have the potential to provide multiple biomarkers for cancers
for early and rapid detection. With newer technologies advancing rapidly,
it may be possible to see a day when liquid biopsies become a routine test for
preventive cancer screening.
- Mattox, Austin K., Chetan Bettegowda, Shibin Zhou, Nickolas Papadopoulos, Kenneth W. Kinzler, and Bert Vogelstein. “Applications of liquid biopsies for cancer.” Science translational medicine 11, no. 507 (2019). Accessed on 9 September 2019 from DOI: https://doi.org/10.1126/scitranslmed.aay1984