Recent Advances in Device Engineering and Computational Analysis for Characterization of Cell-Released Cancer Biomarkers

Abstract

During cancer progression, tumors shed different biomarkers into the bloodstream, including circulating tumor cells (CTCs), extracellular vesicles (EVs), circulating cell-free DNA (cfDNA), and circulating tumor DNA (ctDNA). The analysis of these biomarkers in the blood, known as ‘liquid biopsy’ (LB), is a promising approach for early cancer detection and treatment monitoring, and more recently, as a means for cancer therapy. Previous reviews have discussed the role of CTCs and ctDNA in cancer progression; however, ctDNA and EVs are rapidly evolving with technological advancements and computational analysis and are the subject of enormous recent studies in cancer biomarkers. In this review, first, we introduce these cell-released cancer biomarkers and briefly discuss their clinical significance in cancer diagnosis and treatment monitoring. Second, we present conventional and novel approaches for the isolation, profiling, and characterization of these markers. We then investigate the mathematical and in silico models that are developed to investigate the function of ctDNA and EVs in cancer progression. We convey our views on what is needed to pave the way to translate the emerging technologies and models into the clinic and make the case that optimized next-generation techniques and models are needed to precisely evaluate the clinical relevance of these LB markers.

Diagnostic value of liquid biopsy in the era of precision medicine: 10 years of clinical evidence in cancer

“…Even if they were discovered many decades ago, only in the last years they have captured the attention of scientific community as useful diagnostic tools, due to the diffusion of commercial and homemade liquid biopsy tests [10]. In fact, the development of sequencing technologies and the improvement of cancer genomic knowledge [11] lead to the diffusion of several comprehensive genomic profiling assays to personalize cancer patients' management, promoting the diffusion of liquid biopsy.…”

“…In the last years, many commercial isolation kits have been developed trying to save time but with high costs [102]. Despite these limitations, EVs have been used as a novel biomarker in liquid biopsy for cancer monitoring, staging, and as a prognostic and dynamic tool for cancer therapy management [10,[93][94][95][103][104][105][106][107]. However, the advantage of EV application to clinical settings is related to their various cargoes, allowing the identification of different and more specific molecular targets necessary for a personalized treatment [93][94][95].…”

“…However, the advantage of EV application to clinical settings is related to their various cargoes, allowing the identification of different and more specific molecular targets necessary for a personalized treatment [93][94][95]. The most common EV marker is the RNA and, in particular, the miRNA signature as predictive biomarker of prognosis and survival in different tumors, such as lung [108][109][110], liver [111,112], colorectal [113], prostate [114], hepatocellular [115], breast [116], and pancreatic [117] cancers [10] and glioma [118]. For their nature and role, EVs can also be used to target tumor cells and to deliver and transfer drugs such as chemotherapies or immunotherapies in other cancer cells [10,[119][120][121].…”

“…The most common EV marker is the RNA and, in particular, the miRNA signature as predictive biomarker of prognosis and survival in different tumors, such as lung [108][109][110], liver [111,112], colorectal [113], prostate [114], hepatocellular [115], breast [116], and pancreatic [117] cancers [10] and glioma [118]. For their nature and role, EVs can also be used to target tumor cells and to deliver and transfer drugs such as chemotherapies or immunotherapies in other cancer cells [10,[119][120][121]. For these reasons, recently, EVs are recognized as a promising potential liquid biopsy resource in oncology, but standardized and convenient methods for isolation are needed [91,122].…”

High-throughput sheath-less microfluidic impedance cytometry for point of care applications

“…Over the past two decades, micro uidics has emerged as a promising technology that could replace bulky instruments, reduce material costs, and advance point-of-care therapeutics [4,9]. While paper-based micro uidics is lightweight and portable, it is often not suitable for precise cell quanti cation [10].…”