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.
Highlights
Advances in the field of genomics, proteomics, and other high-throughput methods for biomarker determination have enabled the era of personalized medicine
One of the biggest breakthroughs in personalized medicine was in the Abbreviations: ABC, ATP-binding cassette; bp, base pair; Cell-free DNA (cfDNA), cell-free DNA; CML, chronic myeloid leukemia; CPOC, clinical pharmacogenetics implementation consortium; CTC, circulating tumor cell; ctDNA, circulating tumor DNA; ctRNA, circulating tumor RNA; cytochromes P450 (CYP), cytochromes; Dutch Pharmacogenetics Working Group (DPWG), dutch pharmacogenetics working group; EGFR, epidermal growth factor receptor; EMA, European Medicines Agency; EV, extracellular vesicle; FDA, Food and Drug Administration; GIST, gastrointestinal stromal tumor; MAPK, mitogen-activated protein kinase; NSCLC, non-small cell lung cancer; PDAC, pancreatic ductal adenocarcinoma; UGT, UDP-glucuronosyltransrease; VIP, very important pharmacogene
As several genes associated with targeted therapy, chemotherapy or hormonal therapy were already detected in EVs, they might be used for fine-tuning personalized cancer treatment
Summary
Advances in the field of genomics, proteomics, and other high-throughput methods for biomarker determination have enabled the era of personalized medicine. A limited number of clinical studies investigated EVs to monitor cancer progression, tumor evolution or drug resistance and several putative protein and RNA biomarkers were identified (An et al, 2015; González and Falcón-Pérez, 2015; Dhondt et al, 2018; Vasconcelos et al, 2019).
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