The tumour trail left in blood

Rae, Kelly

doi:10.1038/532269a

Cited by 89 publications

(58 citation statements)

References 8 publications

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“…Within the cardiovascular area, exosomes were reported to exert direct actions on cultured cardiac myocytes, including promoting hypertrophy 14 and survival 15 . Some pioneering human studies on circulating exosomes have focused at finding new clinical biomarkers, particularly in the oncology area, in which the concept of exosomes as “liquid biopsies” enriched with cancer cell-derived factors is receiving attention 16 . However, the characterization of the exosomes present in human biological fluids and their possible role as cell-to-cell communicators of cardiovascular relevance is still undeveloped.…”

Section: Introductionmentioning

confidence: 99%

Human Pericardial Fluid Contains Exosomes Enriched with Cardiovascular-Expressed MicroRNAs and Promotes Therapeutic Angiogenesis

et al. 2017

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The pericardial fluid (PF) is contained in the pericardial sac surrounding the heart. MicroRNA (miRNA) exchange via exosomes (endogenous nanoparticles) contributes to cell-to-cell communication. We investigated the hypotheses that the PF is enriched with miRNAs secreted by the heart and that it mediates vascular responses through exosome exchange of miRNAs. The study was developed using leftover material from aortic valve surgery. We found that in comparison with peripheral plasma, the PF contains exosomes enriched with miRNAs co-expressed in patients’ myocardium and vasculature. At a functional level, PF exosomes improved survival, proliferation, and networking of cultured endothelial cells (ECs) and restored the angiogenic capacity of ECs depleted (via Dicer silencing) of their endogenous miRNA content. Moreover, PF exosomes improved post-ischemic blood flow recovery and angiogenesis in mice. Mechanistically, (1) let-7b-5p is proangiogenic and inhibits its target gene, TGFBR1, in ECs; (2) PF exosomes transfer a functional let-7b-5p to ECs, thus reducing their TGFBR1 expression; and (3) let-7b-5p depletion in PF exosomes impairs the angiogenic response to these nanoparticles. Collectively, our data support the concept that PF exosomes orchestrate vascular repair via miRNA transfer.

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Section: Introductionmentioning

confidence: 99%

Human Pericardial Fluid Contains Exosomes Enriched with Cardiovascular-Expressed MicroRNAs and Promotes Therapeutic Angiogenesis

et al. 2017

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“…An integral part of MASTER is the prospective identification of biomarkers to predict the therapeutic activity of targeted therapies in genetically defined patient cohorts, which will help us evaluate their efficacy across different cancer entities during upcoming clinical trials. We are hopeful that we can achieve our goals more rapidly by multiplex evaluation of multiple circulating biomarkers, such as cell‐free tumor DNA, exosomes or tumor cells . These may allow for a more precise and dynamic measurement of cancer evolution during therapy and may be better suited for assessing its spatial and temporal heterogeneity, as well as monitoring the emergence of molecular resistance mechanisms .…”

Section: Current and Future Developmentsmentioning

confidence: 99%

“…We are hopeful that we can achieve our goals more rapidly by multiplex evaluation of multiple circulating biomarkers, such as cell-free tumor DNA, exosomes or tumor cells. 42 These may allow for a more precise and dynamic measurement of cancer evolution during therapy and may be better suited for assessing its spatial and temporal heterogeneity, as well as monitoring the emergence of molecular resistance mechanisms. 43,44 "Liquid biopsies" based on detection of circulating, cell-free DNA are one of such promising avenues, able to assess the mutation status and the occurrence of resistance mutations, possibly reducing the need for repeated tumor biopsies.…”

Section: Assessment Of Circulating Biomarkersmentioning

confidence: 99%

Precision oncology based on omics data: The NCT Heidelberg experience

Horak

Klink

Heining

et al. 2017

Intl Journal of Cancer

138

117

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Precision oncology implies the ability to predict which patients will likely respond to specific cancer therapies based on increasingly accurate, high-resolution molecular diagnostics as well as the functional and mechanistic understanding of individual tumors. While molecular stratification of patients can be achieved through different means, a promising approach is next-generation sequencing of tumor DNA and RNA, which can reveal genomic alterations that have immediate clinical implications. Furthermore, certain genetic alterations are shared across multiple histologic entities, raising the fundamental question of whether tumors should be treated by molecular profile and not tissue of origin. We here describe MASTER (Molecularly Aided Stratification for Tumor Eradication Research), a clinically applicable platform for prospective, biology-driven stratification of younger adults with advanced-stage cancer across all histologies and patients with rare tumors. We illustrate how a standardized workflow for selection and consenting of patients, sample processing, whole-exome/genome and RNA sequencing, bioinformatic analysis, rigorous validation of potentially actionable findings, and data evaluation by a dedicated molecular tumor board enables categorization of patients into different intervention baskets and formulation of evidence-based recommendations for clinical management. Critical next steps will be to increase the number of patients that can be offered comprehensive molecular analysis through collaborations and partnering, to explore ways in which additional technologies can aid in patient stratification and individualization of treatment, to stimulate clinically guided exploratory research projects, and to gradually move away from assessing the therapeutic activity of targeted interventions on a case-by-case basis toward controlled clinical trials of genomics-guided treatments.

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“…About 25% have an aggressive cancer at the time of diagnosis, with metastatic spread to axillary lymph nodes. 1 Spread is detected by a sentinel node biopsy: a surgical procedure to check the lymph nodes closest to the cancer site for metastasized cancer. A cancer that has developed to the point of metastasis is much more dangerous than a local one.…”

Section: Introductionmentioning

confidence: 99%

Stratified time-course gene preselection shows a pre-diagnostic transcriptomic signal for metastasis in blood cells: a proof of concept from the NOWAC study

Holsbø¹,

Perduca

Bongo³

et al. 2017

Preprint

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In this article we use gene expression measurements from blood samples to predict breast cancer metastasis. We compare several predictive models and propose a biologically motivated variable selection scheme.Curve selection is based on the assumption that gene expression intensity as a function of time should diverge between cases and controls: there should be a larger difference between case and control closer to diagnosis than years before. We obtain better predictions and more stable predictive signatures by using curve selection and show some evidence that metastasis can be detected in blood samples.

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The tumour trail left in blood

Cited by 89 publications

References 8 publications

Human Pericardial Fluid Contains Exosomes Enriched with Cardiovascular-Expressed MicroRNAs and Promotes Therapeutic Angiogenesis

Human Pericardial Fluid Contains Exosomes Enriched with Cardiovascular-Expressed MicroRNAs and Promotes Therapeutic Angiogenesis

Precision oncology based on omics data: The NCT Heidelberg experience

Stratified time-course gene preselection shows a pre-diagnostic transcriptomic signal for metastasis in blood cells: a proof of concept from the NOWAC study

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