Page 11 - ITPS-7-1

INNOSC Theranostics and
Pharmacological Sciences Liquid biopsy and digital PCR in cancer

same mutation is good news for patients with melanoma, A great difficulty in the therapeutic follow-up of solid
since it can be actionable with specific ITKs with very good tumors is the limitation in repeatedly acquiring tissue
results, but it becomes a biomarker of poor prognosis in biopsies from the same patient during the course of tumor
colon cancer, where said ITKs have no effect . Moreover, evolution, especially if the site of tumor reappearance is
[29]
V600E is present in all hairy cell leukemia cases, serving as clinically critical and there is no adequate access to it, or
a marker of minimal residual disease of said hematological surgery acted on the tumor would leave serious sequelae or
neoplasia . The pharmacogenetic characterization even put the patient in life-threatening situation.
[30]
of a tumor, from the very moment a biopsy sample is A new biomarker concept known as “LB” can partially
obtained and prior to the start of any treatment, makes solve this dilemma. LB is a reflection of the genetic
it possible to obtain the so-called genetic fingerprint and information possessed by all types of cells (normal and
identify its possible therapeutic targets. Given the large pathological) or generated by all tissues, and that is
number of molecular variants described, high-throughput poured into the bloodstream and fluid in our body. Like
methodologies such as next-generation sequencing are all biological materials, it will have its elimination kinetics
the most appropriate tools for obtaining said fingerprint since it will be continuously degraded and replaced in the
of each tumor, even from within each cell subclone of the circulation as a result of the balance between production
same tumor [31,32] . In the aforementioned genetic footprint, and elimination. The quantity, quality, and identity of
we can, in turn, establish a biomarker map that provides this biological material provide an idea of its origin and
us with different levels of information, such as tumor clonality, and are proportional to the mass of the tissue
identity, aggressiveness, prognosis, drug sensitivity and that produces it. It can come from normal senescent
resistance, and monitor its therapeutic evolution due to cells, or from necrotic cells destroyed by the immune-
decay (sensitivity) of the initial clone, or its relapse due
to the appearance of a clone with new escape mutations macrophage system, and be detected as free circulating
genetic material (microRNA, DNA, RNA) . Genetic
[36]
(resistance) to the pharmacological pressure exerted.
material may be presented in an encapsulated form within
In turn, we must remember what was initially microvesicles, known as exosomes, actively secreted by
mentioned about the ABC-t. ITKs are substrates of ABC-t. both normal and tumor cells, which travel laden with
A series of preclinical and clinical studies have shown that adhesion molecules, enzymes, structural proteins, and
ABC-t can influence the bioavailability of several TKIs, specific genetic material [37] (Figure 4).
modifying their pharmacokinetics and also playing a role
in the development of resistance to this type of therapy, but In addition, the circulating tumor cells (CTC) are
that in turn, the ITKs can also inhibit ABC-t [33,34] . part of the concept of liquid biopsy. CTC undoubtedly
contain 100% of the genetic information of each tumor,
ABC-t gene polymorphisms can induce significant but their presence is relatively rare in the circulation and
differences of therapeutic responses in the same pathology it is extremely difficult to detect them. Together, all the
with the same TK mutations treated with the same ITK. circulating genetic material can be isolated, amplified, and
properly deciphered, providing much of the information
4. Liquid biopsy (LB), the ideal biomarker corresponding to the cells present in the tumor of origin.
Since the early report by Vietsch et al., circulating tumor LB provides very valuable information regarding the
DNA and micro-RNA (later named as “LB”) have been presence of somatic mutations that are pharmacologically
used as cancer diagnostic tools . Today, there are more actionable and mutations that are resistant to current
[35]
than 12,000 reports on LB on PubMed database. available therapeutics. These genetic information can be
The process searching for the ideal biomarker provides used as a biomarker of minimal residual disease, and as
us with extensive information regarding the pathology a theranostics tool to evaluate therapeutic behavior, such
of cancer. For this, the ideal biomarker must provide as optimal, suboptimal, or null response. In addition, LB
diagnostic, prognostic, and therapeutic information. The allows for early detection of tumor or its relapse of tumor
genesis and stability of the biomarker must reflect the harboring genetic variants resistant to the first treatment,
kinetics of cancer evolution, and it should be quantitatively even before the onset of clinical symptoms and/or its
representative of tumor size or mass. In addition, its detection by imaging methods. This early detection reduces
sampling must be accessible and repeatable without the risk of tumor evolution, improving the patient’ life
involving invasive, risky procedures on the patients. quality, and increase the event-free survival time. However,
Importantly, the ideal biomarker must be highly sensitive the main limitation of LB is that it cannot identify the site
and highly specific, surpassing the qualities seen in the where the tumor is growing, or whether it is a primary or
classical clinical biochemical methods (Figure 3). metastatic tumor.

Volume 7 Issue 1 (2024) 5 https://doi.org/10.36922/itps.1227