Clinical Utility of Liquid Biopsy-Based Actionable Mutations Detected via ddPCR

Abstract

Cancer is one of the leading causes of death worldwide and remains a major public health challenge. The introduction of more sensitive and powerful technologies has permitted the appearance of new tumor-specific molecular aberrations with a significant cancer management improvement. Therefore, molecular pathology profiling has become fundamental not only to guide tumor diagnosis and prognosis but also to assist with therapeutic decisions in daily practice. Although tumor biopsies continue to be mandatory in cancer diagnosis and classification, several studies have demonstrated that liquid biopsies could be used as a potential tool for the detection of cancer-specific biomarkers. One of the main advantages is that circulating free DNA (cfDNA) provides information about intra-tumoral heterogeneity, reflecting dynamic changes in tumor burden. This minimally invasive tool has become an accurate and reliable instrument for monitoring cancer genetics. However, implementing liquid biopsies across the clinical practice is still ongoing. The main challenge is to detect genomic alterations at low allele fractions. Droplet digital PCR (ddPCR) is a powerful approach that can overcome this issue due to its high sensitivity and specificity. Here we explore the real-world clinical utility of the liquid biopsy ddPCR assays in the most diagnosed cancer subtypes.

Potential utility of miRNAs for liquid biopsy in breast cancer

“…Additionally, in LB, invasiveness and residual disease are minimized that also enables and simplifies the longitudinal monitoring of BC patients. LB potentiates obtaining the complete molecular picture of the tumor and, thus, enhances more precise clinical decisions ( 5 , 77 ). Indeed, a number of studies successfully consolidate the significance of LB in BC ( 78 – 81 ) and other cancers too ( 82 , 83 ).…”

Liquid biopsy to detect resistance mutations against anti-epidermal growth factor receptor therapy in metastatic colorectal cancer

“…Nucleic acids can be detected by polymerase chain reaction (PCR)-based techniques or next-generation sequencing (NGS)[ 19 ]. The advantages of PCR-based techniques include their lower cost, shorter processing time, and easier bioinformatics analysis than NGS techniques[ 20 ]. Disadvantages of PCR techniques include the selection of a prior bound study target and the difficulty in examining rare genetic alterations[ 21 ].…”

Liquid Biopsy: A New Translational Diagnostic and Monitoring Tool for Musculoskeletal Tumors

“…By capturing the molecular landscape of a tumor, as well as detecting possible molecular changes in tumor cells, personalized treatment regimens can be developed that will uttermost benefit patients' outcome. Moreover, aggressive tumor types and potential drug resistance can be assessed through molecular profiling of tumor cells [9]. Lastly, treatment monitoring through measurement of blood levels of certain biomarkers, which can exhibit stability or increase in cases of treatment resistance, can prove a useful tool in the clinical setting [10].…”