Pharmacogenetic and liquid biopsy: The new tools of precision medicine in cancer

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 to these targeted therapies coexist in the same tumor, from the start of therapy or as a consequence of the first-line treatment. The mutations in circulating DNA in body fluids, which are detected and quantified by droplet digital polymerase chain reaction-assisted liquid biopsy, are the ideal biomarkers for the evaluation of pharmacological response, which is crucial for facilitating the change of therapeutic strategy involving second- or third-generation drugs. The quantification of these mutations can be used to assess minimal residual disease in the therapeutic follow-up of each case.