Extracellular Vesicles: A Novel Tool Facilitating Personalized Medicine and Pharmacogenomics in Oncology

Abstract

Biomarkers that can guide cancer therapy based on patients’ individual cancer molecular signature can enable a more effective treatment with fewer adverse events. Data on actionable somatic mutations and germline genetic variants, studied by personalized medicine and pharmacogenomics, can be obtained from tumor tissue or blood samples. As tissue biopsy cannot reflect the heterogeneity of the tumor or its temporal changes, liquid biopsy is a promising alternative approach. In recent years, extracellular vesicles (EVs) have emerged as a potential source of biomarkers in liquid biopsy. EVs are a heterogeneous population of membrane bound particles, which are released from all cells and accumulate into body fluids. They contain various proteins, lipids, nucleic acids (miRNA, mRNA, and DNA) and metabolites. In cancer, EV biomolecular composition and concentration are changed. Tumor EVs can promote the remodeling of the tumor microenvironment and pre-metastatic niche formation, and contribute to transfer of oncogenic potential or drug resistance during chemotherapy. This makes them a promising source of minimally invasive biomarkers. A limited number of clinical studies investigated EVs to monitor cancer progression, tumor evolution or drug resistance and several putative EV-bound protein and RNA biomarkers were identified. This review is focused on EVs as novel biomarker source for personalized medicine and pharmacogenomics in oncology. As several pharmacogenes and genes associated with targeted therapy, chemotherapy or hormonal therapy were already detected in EVs, they might be used for fine-tuning personalized cancer treatment.

Blood Nanoparticles – Influence on Extracellular Vesicle Isolation and Characterization

“…Much less is known about EV-associated DNA, although it appears that the DNA can be located in the EV lumen or attached to the surface of EVs as single or double-stranded molecules that are protected from degradation by the bound histones. EV-associated DNA is also heterogeneous in origin (i.e., genomic, mitochondrial) and size (i.e., a few hundred base pairs in small EVs, up to >2 million base pairs in large EVs) ( Goričar et al, 2021 ). EVs protect the nucleic acids from degradation by nucleases that are commonly present in biological fluids, making them remarkably stable under different storage conditions.…”

Sampling, Logistics, and Analytics of Urine for RT-qPCR-based Diagnostics

“…In the field of cancer diagnostics, non-invasive technologies are increasingly attractive for initial diagnosis of tumors and for therapy monitoring [1][2][3]. Body fluids are the primary source of liquid biopsy, i.e., biomarker detection, and include blood and serum, urine, and saliva [4,5]. In most body fluids and in urine, in particular, nucleic acids can be found in subcompartments and in extracellular vesicles that can be isolated including circulating tumor cells (CTC's), exosome-like particles, ectosome-like particles, and apoptotic bodies [6][7][8][9][10][11].…”

Circulating galectin-3 promotes tumor-endothelium-adhesion by upregulating ICAM-1 in endothelium-derived extracellular vesicles

“…As EVs has been reported to involve in tumor progression ( Goričar et al, 2021 ; Wu et al, 2021 ; Thakur et al, 2022 ), the detection of EVs as diagnostic and diagnostic biomarkers of tumor ( Thakur et al, 2020a ; Qu et al, 2021 ; Xu et al, 2021 )and EVs based drug delivery systems ( Thakur et al, 2020b ; Gaurav et al, 2021 ) has attracted extensive attention. Further research on its regulatory effects on tumor metastasis and underlying mechanism will be beneficial to its clinical application.…”