The potential of circulating nucleic acids as components of companion diagnostics for predicting and monitoring chemotherapy response

Abstract

An effective personalized medicine is associated with the ability of identifying cancer patients who respond to anticancer targeted therapies. Therefore, new companion biomarkers that facilitate drug development are urgently needed. Since clinically relevant genetic and epigenetic alterations can be detected in cell-free nucleic acids in the blood circulation of cancer patients, these molecules may be a new promising class of potential liquid biomarkers. They can be obtained in real-time from blood, and their analyses could, consequently, facilitate treatment decisions. Screening of these liquid biopsies may provide information on the aberrant signaling pathway that should be blocked by the chosen targeted therapy. This article will discuss the potential of circulating nucleic acids as therapeutics for overcoming chemotherapeutic resistance in anticancer strategies.

MicroRNAs and Their Impact on Radiotherapy for Cancer

“…Recent studies have also detected so-called ''circulating miRNAs'' in blood samples. These circulating miRNAs, which are present in stable forms in the blood stream, might be detectable as clinical biomarkers (40). Radiationinduced changes in blood-based miRNA expression profiles have recently been reported.…”

The clinical relevance of circulating, exosomal miRNAs as biomarkers for cancer

“…The detection of exosomes is usually carried out by Western blot or flow cytometry using antibodies specific for diverse exosomal markers, for example, CD9, CD63 or CD81 [30]. Currently, diverse detection methods for miRNAs, including a variety of quantitative PCR techniques, northern blotting, in situ hybridization, microarray and deep sequencing, are used [16,31]. Quantitative real-time PCR is the gold standard to quantify miRNAs.…”

“…Since miRNAs loci frequently map to fragile chromosomal regions harboring DNA amplifications, deletions or translocations, their expression is often deregulated during tumorigenesis, contributing to tumor progression and metastasis [15]. Rising evidence suggests that dysregulated miRNAs may be involved in the acquisition of resistance to chemotherapy by modulating the drug sensitivity of cancer cells [4,16].…”

Methods: for studying pharmacogenetic profiles of combination chemotherapeutic drugs

“…Furthermore, in order to personalize therapeutic regimens [100] and to anticipate the occurrence of drug resistance [101], the tumor mutational status may be investigated by NGS on CTC or ctDNA over time. For example, the increasing number of mutant alleles or the occurrence of gene amplification as resulted from ctDNA was associated with the emergence of drug resistance in patients affected by solid tumors [102,103].…”