Accession of Tumor Heterogeneity by Multiplex Transcriptome Profiling of Single Circulating Tumor Cells

Gorges, Tobias M.; Kuske, Andra; Röck, Katharina; Mauermann, Oliver; Müller, Volkmar; Peine, Sven; Verpoort, Karl; Novosadová, Vendula; Kubista, Mikael; Riethdorf, Sabine; Pantel, Klaus

doi:10.1373/clinchem.2016.260299

Cited by 131 publications

(129 citation statements)

References 36 publications

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“…The relative rarity of CTCs in patients, especially at early disease stages, should also bring our attention to the representativeness of molecular characteristics of the few captured cells. Single-cell genomics [180][181][182][183] and transcriptomics [41,138,180,182,184] revealed significant interpatient molecular heterogeneity among CTCs.…”

Section: Resultsmentioning

confidence: 99%

The Landscape of Circulating Tumor Cell Research in the Context of Epithelial-Mesenchymal Transition

Markiewicz

Żaczek²

2017

Pathobiology

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The metastatic spread of cancer accounts for the vast majority of cancer-related deaths. It is mediated by tumor cells circulating in blood (called circulating tumor cells, CTCs), which escaped from their established niches. CTCs give a unique opportunity to look into the metastatic cascade and to study the molecular processes supporting the spread of tumor cells throughout the body. As current therapies are not sufficiently effective in treating metastatic disease, it is important to determine cellular and molecular features of cancer cells that “seed” new tumors in distant organs at early stages. In this review we focus on the role of the epithelial-mesenchymal transition program in providing a survival advantage to metastasizing tumor cells, especially CTCs, and put it in the context of clinical findings.

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Section: Resultsmentioning

confidence: 99%

The Landscape of Circulating Tumor Cell Research in the Context of Epithelial-Mesenchymal Transition

Markiewicz

Żaczek²

2017

Pathobiology

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“…Recently reported profiling studies continue to elucidate the genomic complexity of cancer. Most are observational and are not reported as biomarkers that can be associated with clinical outcomes or used to impact medical decision making in patients (11,12). Here, we report the development of a quantitative biomarker of CTC heterogeneity fit-for-purpose (13) of informing treatment selection at the time a change in therapy is needed, and explore the relationship between CTC phenotypic heterogeneity and patient survival following treatment with androgen receptor signaling inhibitors (ARSI) or taxane chemotherapies.…”

Section: Introductionmentioning

confidence: 99%

Phenotypic Heterogeneity of Circulating Tumor Cells Informs Clinical Decisions between AR Signaling Inhibitors and Taxanes in Metastatic Prostate Cancer

et al. 2017

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The heterogeneity of an individual patient’s tumor has been linked to treatment resistance, but quantitative biomarkers to rapidly and reproducibly evaluate heterogeneity in a clinical setting are currently lacking. Using established tools available in a CAP-accredited and CLIA-certified clinical laboratory, we quantified digital pathology features on 9,225 individual circulating tumor cells (CTCs) from 179 unique metastatic castration-resistant prostate cancer (mCRPC) patients to define phenotypically distinct cell types. Heterogeneity was quantified based on the diversity of cell types in individual patient samples using the Shannon index and associated with overall survival (OS) in the 145 specimens collected prior to initiation of second or later lines of therapy. Low CTC phenotypic heterogeneity was associated with better OS in patients treated with androgen receptor signaling inhibitors (ARSI), whereas high heterogeneity was associated with better OS in patients treated with taxane chemotherapy. Overall, the results show that quantifying CTC phenotypic heterogeneity can help inform the choice between ARSI and taxanes in mCRPC patients.

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“…In this context, the detection of tissue-specific gene expression in CTCs [30] might be a promising approach.…”

Section: Discussionmentioning

confidence: 99%

Blood-Based Analysis of Circulating Cell-Free DNA and Tumor Cells for Early Cancer Detection

Pantel

2016

PLoS Med

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Accession of Tumor Heterogeneity by Multiplex Transcriptome Profiling of Single Circulating Tumor Cells

Abstract: Multimarker RNA profiling of single CTCs reveals distinct CTC subsets and provides important insights into gene regulatory networks relevant for cancer progression and therapy.

Cited by 131 publications

References 36 publications

The Landscape of Circulating Tumor Cell Research in the Context of Epithelial-Mesenchymal Transition

The Landscape of Circulating Tumor Cell Research in the Context of Epithelial-Mesenchymal Transition

Phenotypic Heterogeneity of Circulating Tumor Cells Informs Clinical Decisions between AR Signaling Inhibitors and Taxanes in Metastatic Prostate Cancer

Blood-Based Analysis of Circulating Cell-Free DNA and Tumor Cells for Early Cancer Detection

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