EGFR detection in extracellular vesicles of breast cancer patients through immunosensor based on silica-chitosan nanoplatform

Ortega, Francisco G.; Piguillem, Sofía V.; Messina, Germán A.; Tortella, Gonzalo; Rubilar, Olga; Castillo, María I. Jiménez; Lorente, José A.; Serrano, María José; Raba, Julio; Fernández‐Baldo, Martín A.

doi:10.1016/j.talanta.2018.10.016

Cited by 34 publications

(20 citation statements)

References 35 publications

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“…The high abundance of circulating EVs and a biological composition reflecting the cell of origin [11] qualify them as attractive diagnostic tool [12]. This potential has been recently demonstrated from liquid biopsies by detecting cancer biomarkers with recognized clinical utility, for example in the case of circulating levels of EGFR in lung cancer [13] and breast cancer [14] patients or EGFR mutations in pulmonary adenocarcinoma patients [14,15]; in the case of KRAS G12D and TP53 R273H mutations in patients with advanced or early-stage pancreatic cancer [16,17]; in the case of copy number variations that matched genes frequently altered in metastatic prostate cancer patients [18].…”

Section: Introductionmentioning

confidence: 99%

Ultrasensitive detection of cancer biomarkers by nickel-based isolation of polydisperse extracellular vesicles from blood

et al. 2019

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Background Extracellular vesicles (EVs) are secreted membranous particles intensively studied for their potential cargo of diagnostic markers. Efficient and cost-effective isolation methods need to be established for the reproducible and high-throughput study of EVs in the clinical practice. Methods We designed the nickel-based isolation (NBI) to rapidly isolate EVs and combined it with newly-designed amplified luminescent proximity homogeneous assay or digital PCR to detect biomarkers of clinical utility. Findings From plasma of 46 healthy donors, we systematically recovered small EV (~250 nm of mean diameter; ~3 × 10 10 /ml) and large EV (~560 nm of mean diameter; ~5 × 10 8 /ml) lineages ranging from 50 to 700 nm, which displayed hematopoietic/endothelial cell markers that were also used in spike-in experiments using EVs from tumor cell lines. In retrospective studies, we detected picomolar concentrations of prostate-specific membrane antigen (PSMA) in fractions of EVs isolated from the plasma of prostate cancer patients, discriminating them from control subjects. Directly from oil-encapsulated EVs for digital PCR, we identified somatic BRAF and KRAS mutations circulating in the plasma of metastatic colorectal cancer (CRC) patients, matching 100% of concordance with tissue diagnostics. Importantly, with higher sensitivity and specificity compared with immuno-isolated EVs, we revealed additional somatic alterations in 7% of wild-type CRC cases that were subsequently validated by further inspections in the matched tissue biopsies. Interpretation We propose NBI-combined approaches as simple, fast, and robust strategies to probe the tumor heterogeneity and contribute to the development of EV-based liquid biopsy studies. Fund Associazione Italiana per la Ricerca sul Cancro (AIRC), Fondazione Cassa di Risparmio Trento e Rovereto (CARITRO), and the Italian Ministero Istruzione, Università e Ricerca (Miur).

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Section: Introductionmentioning

confidence: 99%

Ultrasensitive detection of cancer biomarkers by nickel-based isolation of polydisperse extracellular vesicles from blood

et al. 2019

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“…Currently, monoclonal humanized antibodies (cetuximab, panitumumab) or tyrosine kinase inhibitors (e.g., erlotinib) targeting oncogenic EGFR show limited response and frequently evoke resistance in patients (Sebastian et al, 2006;Sigismund et al, 2018). Liquid biopsy, more specifically EVs, could contribute to improved cancer progression and therapy follow-up, as EVs containing EGFR DNA, RNA or protein were detected in blood, cerebrospinal fluid, bronchoalveolar lavage or pleural effusions in different cancers (Table 1), which in some studies correlated with prognosis (Skog et al, 2008;Shao et al, 2012;Yamashita et al, 2013;Figueroa et al, 2017;Castellanos-Rizaldos et al, 2018;Krug et al, 2018;Wan et al, 2018;Ortega et al, 2019;Qu et al, 2019;Song et al, 2019). For example, anticancer agents blocking oncogenic EGFR (e.g., dacomitinib, canertinib) stimulated the release of EVs carrying EGFRvIII and genomic DNA in glioblastoma animal models and patients (Skog et al, 2008;Montermini et al, 2015;Choi et al, 2019), and in turn, EV-EGFRvIII were shown to fuse with cancer cells lacking EGFRvIII and transfer the oncogenic activity (Al-Nedawi et al, 2008).…”

Section: Egfrmentioning

confidence: 99%

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

2021

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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.

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“…Therefore, the diverse relationship between EGFR and BC stages reflected in different studies could be caused by differences in samples and experimental methods. Previously, Ortega et al (38) used electrochemical sensors to analyze plasma sEV samples from 30 patients with early BC and 20 healthy donors. The results also showed that sEV-EGFR levels were significantly higher in patients with BC than in healthy controls (AUC = 0.902 ± 0.045 SD), which was determined to be more sensitive and specific than traditional serum markers, such as carcinoembryonic antigen and mucin-1.…”

Section: Candidate Ev Proteins For Early Bc Diagnosismentioning

confidence: 99%

Protein biomarkers in breast cancer-derived extracellular vesicles for use in liquid biopsies

Lai

Fan

et al. 2021

American Journal of Physiology-Cell Physiology

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Breast cancer is the most common malignant disease in women worldwide. Early diagnosis and treatment can greatly improve the management of breast cancer. Liquid biopsies are becoming convenient detection methods for diagnosing and monitoring breast cancer due to their non-invasiveness and ability to provide real-time feedback. A range of liquid biopsy markers, including circulating tumor proteins, circulating tumor cells, and circulating tumor nucleic acids, have been implemented for breast cancer diagnosis and prognosis, with each having its own advantages and limitations. Circulating extracellular vesicles are messengers of intercellular communication that are packed with information from mother cells and are found in a wide variety of bodily fluids; thus, they are emerging as ideal candidates for liquid biopsy biomarkers. In this review, we summarize extracellular vesicle protein markers that can be potentially used for the early diagnosis and prognosis of breast cancer or determining its specific subtypes.

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EGFR detection in extracellular vesicles of breast cancer patients through immunosensor based on silica-chitosan nanoplatform

Cited by 34 publications

References 35 publications

Ultrasensitive detection of cancer biomarkers by nickel-based isolation of polydisperse extracellular vesicles from blood

Ultrasensitive detection of cancer biomarkers by nickel-based isolation of polydisperse extracellular vesicles from blood

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

Protein biomarkers in breast cancer-derived extracellular vesicles for use in liquid biopsies

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