Page 7 - ITPS-7-1

INNOSC Theranostics

and Pharmacological Sciences

REVIEW ARTICLE
Pharmacogenetic and liquid biopsy: The new

tools of precision medicine in cancer

Verónica Alejandra Alonso, and Alberto Lazarowski*
INFIBIOC - Clinical Biochemistry Department, School of Pharmacy and Biochemistry, University of
Buenos Aires, Buenos Aires, Argentina

Abstract
The main difficulty in the treatment of cancer lies in the already known mechanism
of resistance to conventional chemotherapy. It is mainly due to the expression of the
multidrug transport systems known as ABC transporters, both in neoplastic cells and
in excretory organs that reduce the chemotherapeutic concentration. The cancer cell
proliferation by activation of growth factor receptors induces their intrinsic tyrosine
kinase activity, and their intracellular signaling pathways involved in such activation.
Tumor proliferation can respond to the direct action of growth factors on their
respective receptors, or due to somatic mutations in different steps of their signaling
pathway, in an independent manner of growth factor stimulus. Pharmacogenetics
studies have been performed to identify these drivers’ mutations and their detection
enables targeted inhibitory therapies against their abnormal proteins. The design of
new molecules capable of inhibiting these signals has opened a new line of treatment
for each type of tumor, thereby enabling tumor growth control and giving rise to the
precision medicine approach. It is possible that mutations of sensitive and resistant
*Corresponding author:
Alberto Lazarowski to these targeted therapies coexist in the same tumor, from the start of therapy or as
(alazarowski@gmail.com) a consequence of the first-line treatment. The mutations in circulating DNA in body
Citation: Alonso VA, Lazarowski A, fluids, which are detected and quantified by droplet digital polymerase chain reaction-
2024, Pharmacogenetic and liquid assisted liquid biopsy, are the ideal biomarkers for the evaluation of pharmacological
biopsy: The new tools of precision response, which is crucial for facilitating the change of therapeutic strategy involving
medicine in cancer. INNOSC
Theranostics and Pharmacological second- or third-generation drugs. The quantification of these mutations can be used
Sciences, 7(1): 1227. to assess minimal residual disease in the therapeutic follow-up of each case.
https://doi.org/10.36922/itps.1227
Received: July 3, 2023 Keywords: Liquid biopsy; Droplet digital polymerase chain reaction; Pharmacogenetics;
Accepted: August 11, 2023 Somatic mutations; Sensitive mutations; Resistant mutations; Minimal residual disease
Published Online: September 11,
2023
Copyright: © 2023 Author(s).
This is an Open-Access article 1. Multidrug resistance (MDR) in cancer
distributed under the terms of the
Creative Commons Attribution Drug resistance in cancer is a common occurrence that refers to therapeutic failure
License, permitting distribution, characterized by tumor relapse with absolute refractory pharmacological behavior to
and reproduction in any medium, classic chemotherapeutics, after the effectiveness of the chemotherapeutics reduces
provided the original work is
properly cited. over time. One of the most characterized mechanisms of this type of response is driven
by a family of genes that encode the MDR proteins or ATP-binding cassette (ABC)-
Publisher’s Note: AccScience
Publishing remains neutral with transporters (ABC-t).
regard to jurisdictional claims in
published maps and institutional These membrane proteins are capable of expelling a wide spectrum of drugs out of
affiliations. cells, even though the drugs have highly diverse molecular structures and are directed

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