New frontiers in circulating tumor cell analysis: A reference guide for biomolecular profiling toward translational clinical use

Becker, Therese M.; Caixeiro, Nicole J.; Lim, Stephanie; Tognela, Annette; Kienzle, Norbert; Scott, Kieran F.; Spring, Kevin; Souza, Paul de

doi:10.1002/ijc.28516

Cited by 32 publications

(25 citation statements)

References 89 publications

(207 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To that end, blood biopsies are becoming increasingly attractive because various tumor-derived biomarkers can be screened from blood. Tumors release entire circulating tumor cells (CTCs) and circulating tumor nucleic acids (ctDNA and ctRNA) into the blood stream, and screening these for tumor associated genetic changes is becoming increasingly feasible [6,7]. While these kinds of assays still need further validation before they can be adopted into clinical practice, blood-based assays are extremely appealing to clinicians and researchers.…”

Section: Introductionmentioning

confidence: 99%

Droplet Digital PCR Based Androgen Receptor Variant 7 (AR-V7) Detection from Prostate Cancer Patient Blood Biopsies

Luk

Young

et al. 2016

IJMS

Self Cite

View full text Add to dashboard Cite

Androgen receptor splice variant V7 (AR-V7) was recently identified as a valuable predictive biomarker in metastatic castrate-resistant prostate cancer. Here, we report a new, sensitive and accurate screen for AR-V7 mRNA expression directly from circulating tumor cells (CTCs): We combined EpCAM-based immunomagnetic CTC isolation using the IsoFlux microfluidic platform with droplet digital polymerase chain reaction (ddPCR) to analyze total AR and AR-V7 expression from prostate cancer patients CTCs. We demonstrate that AR-V7 is reliably detectable in enriched CTC samples with as little as five CTCs, even considering tumor heterogeneity, and confirm detection of AR-V7 in CTC samples from advanced prostate cancer (PCa) patients with AR-V7 detection limited to castrate resistant disease status in our sample set. Sensitive molecular analyses of circulating tumor cells (CTCs) or circulating tumor nucleic acids present exciting strategies to detect biomarkers, such as AR-V7 from non-invasive blood samples, so-called blood biopsies.

show abstract

Section: Introductionmentioning

confidence: 99%

Droplet Digital PCR Based Androgen Receptor Variant 7 (AR-V7) Detection from Prostate Cancer Patient Blood Biopsies

Luk

Young

et al. 2016

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Moreover, the metastatic potential of CTCs may vary [34]. Increased understanding of the high prognostic value of being able to identify CTC subsets capable of generating a metastatic deposit has led to increased interest in development of methods that will enable genomic characterization of individual CTCs and thus facilitate the rational design of targeted anticancer therapies [35, 36]. However most microfluidic chips for isolating CTCs are closed systems, so trapped CTCs from samples are more likely to be lost and recovery of isolated single CTCs is poor.…”

Section: Discussionmentioning

confidence: 99%

Rare cell isolation and recovery on open-channel microfluidic chip

et al. 2017

View full text Add to dashboard Cite

The ability to accurately detect and analyze rare cells in a cell population is critical not only for the study of disease progression but also for next flow cytometry systems in clinical application. Here, we report the development of a prototype device, the ‘Rare cell sorter’, for isolating and recovering single rare cells from whole blood samples. On this device, we utilized an open-channel microfluidic chip for rare cell isolation. And the advantage of open-channel allows us to recover the isolated rare cell directly from the chip. We set the circulating tumor cell (CTC) as a target cell.For the clinical experiment, CTCs were isolated from blood samples collected from patients with metastatic breast cancer and healthy volunteers. There was a significant difference in the number of CTCs between the patients with metastatic breast cancer and healthy volunteers. To evaluate the damage to cells during isolation and recovery, we performed an RNA integrity assay using RNA extracted from CTCs recovered from the chip and found that our process for single CTC isolation and recovery is mild enough for gene analysis of CTCs.

show abstract

“…Research on circulating tumour cells (CTCs) has rapidly increased in the last years in response to the clinical need of new alternative tools for the management of patients candidate for personalized therapeutic strategies12. Traditionally, efforts have been devoted to understand the mechanisms underlying cancer progression mainly focused on primary and metastatic carcinomas; but little is known about the “fluid phase” of cancer as the relevant actor of tumour dissemination and lethality13.…”

Section: Discussionmentioning

confidence: 99%

Molecular Profiling of Circulating Tumour Cells Identifies Notch1 as a Principal Regulator in Advanced Non-Small Cell Lung Cancer

Mariscal

Alonso-Nocelo

Muinelo‐Romay

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Knowledge on the molecular mechanisms underlying metastasis colonization in Non-Small Cell Lung Cancer (NSCLC) remains incomplete. A complete overview integrating driver mutations, primary tumour heterogeneity and overt metastasis lacks the dynamic contribution of disseminating metastatic cells due to the inaccessibility to the molecular profiling of Circulating Tumour Cells (CTCs). By combining immunoisolation and whole genome amplification, we performed a global gene expression analysis of EpCAM positive CTCs from advanced NSCLC patients. We identified an EpCAM+ CTC-specific expression profile in NSCLC patients mostly associated with cellular movement, cell adhesion and cell-to-cell signalling mediated by PI3K/AKT, ERK1/2 and NF-kB pathways. NOTCH1 emerged as a driver connecting active signalling pathways, with a reduced number of related candidate genes (NOTCH1, PTP4A3, LGALS3 and ITGB3) being further validated by RT-qPCR on an independent cohort of NSCLC patients. In addition, these markers demonstrated high prognostic value for Progression-Free Survival (PFS). In conclusion, molecular characterization of EpCAM+ CTCs from advanced NSCLC patients provided with highly specific biomarkers with potential applicability as a “liquid biopsy” for monitoring of NSCLC patients and confirmed NOTCH1 as a potential therapeutic target to block lung cancer dissemination.

show abstract

New frontiers in circulating tumor cell analysis: A reference guide for biomolecular profiling toward translational clinical use

Cited by 32 publications

References 89 publications

Droplet Digital PCR Based Androgen Receptor Variant 7 (AR-V7) Detection from Prostate Cancer Patient Blood Biopsies

Droplet Digital PCR Based Androgen Receptor Variant 7 (AR-V7) Detection from Prostate Cancer Patient Blood Biopsies

Rare cell isolation and recovery on open-channel microfluidic chip

Molecular Profiling of Circulating Tumour Cells Identifies Notch1 as a Principal Regulator in Advanced Non-Small Cell Lung Cancer

Contact Info

Product

Resources

About