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

Figure 2. Schematic representation indicating how a growth factor stimulates its corresponding receptor, which contains an intrinsic tyrosine kinase
(phosphorylated) in its intracytoplasmic domain and triggers a specific signal cascade, sequentially activating different proteins, until reaching the
executing phase of the effect on the nucleus, activating cell proliferation [16,17] . Mutations found in the tyrosine kinases of growth factor receptors as well as
on signaling pathway intermediaries are the entry points for therapy since they are sensitive to the action of first-line specific inhibitors. The presence of
resistant mutations in the same tyrosine kinases forces the use of second- or third-generation drugs directed against said mutations. The identification and
quantification of both types of somatic mutations, which are sensitive and resistant to first-line ITKs, are essential for identifying patients amenable to the
treatment and assisting with the monitoring of tumor evolution.

presence of both types of sensitive and resistant mutations is kinases are found downstream of the signaling pathway
an indication of the heterogeneity of the tumor population arising from EGFR. Thus, the mere presence of any of
that may warrant joint treatment with both types of ITKs these mutations in the KRAS or NRAS genes prevents
simultaneously. If this is the case, we are in the presence therapy with the aforementioned anti-EGFR monoclonal
of two pharmaco genetically distinct populations, which antibodies. This prompts the search for pharmacologically
occupy different percentages of the tumor mass. This duality actionable mutations on other G proteins that are
can exist from the very moment of molecular diagnosis, downstream of the KRAS/NRAS signaling, such as BRAF,
or arise as a consequence of the pharmacological pressure MEK, and mTOR [25-27] . The therapy combining an anti-
exerted by treatment with first-line ITKs that will lead to EGFR monoclonal antibody and an ITK directed at the
gradual apoptosis in the cell clone carrying the sensitive tyrosine kinase mutations of the G-proteins has shown
mutation, giving place or biological space to the growth of encouraging responses in colon cancer, even in the
the cell clone carrying the resistant mutation. presence of KRAS mutations . However, these strategies
[28]
In the event that both the EGFR gene and its entire have failed to show any benefit in NSCLC with the same
specific signaling cascade do not contain any somatic mutation background because the mutations in KRAS,
mutations that drive tumor growth, the therapeutic NRAS, or BRAF (exclusive of each other) may drive the
opportunity will lie in the use of monoclonal antibodies tumor growth, and they are genetic markers of drug
that inhibit and/or block growth factor binding with its resistance, which requires treatment with conventional
specific receptor. Although it has not been possible to chemotherapies [19,20] . It is also possible that we find EGFR
obtain positive results with this therapy in the case of gene mutations, whose biological and/or pharmacological
[22]
NSCLC, it is usually effective in colon cancer [23,24] . action is unknown .
Typically, in colon cancer, the EGFR gene does not have A particular situation arises in the case of the V600E
mutations of any kind, but mutated and activated tyrosine mutation of the BRAF gene, where it was found that this

Volume 7 Issue 1 (2024) 4 https://doi.org/10.36922/itps.1227