An improved CTC isolation scheme for pairing with downstream genomics: Demonstrating clinical utility in metastatic prostate, lung and pancreatic cancer

Premasekharan, Gayatri; Gilbert, Elizabeth; Okimoto, Ross A.; Hamirani, Ashiya; Lindquist, Karla; Ngo, Vy; Roy, Ritu; Hough, Jeffrey; Edwards, Matthew R.; Paz, Rosa; Foye, Adam; Sood, Riddhi; Copren, Kirsten A.; Gubens, Matthew A.; Small, Eric J.; Bivona, Trever G.; Collisson, Eric A.; Friedlander, Terence W.; Paris, Pamela L.

doi:10.1016/j.canlet.2016.06.017

Cited by 25 publications

(18 citation statements)

References 57 publications

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“…We believe that there should be a difference according to the nodule size and that such a difference might be detected with a modification of the methods of determining the CTC counts and more patients with SPN. Premasekharan et al proposed that by using downstream genomics in patients with metastatic lung cancer, improvements can be made in CTC isolation [29]. Although such parameters may have influenced the results, further investigations are required to assess the effect of the detection method on the number of CTCs in patients with SPNs [30,31].…”

Section: Discussionmentioning

confidence: 99%

The combination of CTCs and CEA can help guide the management of patients with SPNs suspected of being lung cancer

et al. 2020

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Objective: Solitary pulmonary nodules (SPNs) is a common radiographic finding and require further evaluation because of the possibility of lung cancer. This study aimed to determine the sensitivity and specificity of circulating tumour cells (CTCs) as a marker for the diagnosis of SPNs and the integration of CTCs, carcinoembryonic antigen (CEA) and imaging findings to improve the sensitivity and specificity of diagnosis in patients with SPNs suspected of being lung cancer. Method: For the serum biomarker assay, the concentration of CEA was measured by an automated electrochemiluminescence analyzer. CTCs were collected from 6 ml of blood by the SE i-FISH method, which detects the gene copy number in eight chromosomes and the tumour-associated antigen CK18. Results: With a threshold of 6 CTC units, the method showed a sensitivity of 67.1% and a specificity of 56.5% in the diagnosis of NSCLC, especially in the upper lobe, in which the diagnostic strength was the highest (P < 0.01). CTCs, CEA and nodule type had the highest diagnostic efficacy (area under the curve, 0.827; 95% confidence interval, 0.752-0.901) in patients with SPNs being suspected lung cancer. Combining CTCs (cut-off value 12 units) with CEA (1.78 ng/ml), the method showed a sensitivity of 77.8% and a specificity of 90% in the diagnosis of NSCLC, especially in the upper lobe, subsolid nodules and nodules ≥8 mm. Conclusions: Our results demonstrated that CTCs are feasible diagnostic biomarkers in patients with SPNs, especially in the upper lobe. Furthermore, CTCs combined with CEA showed higher diagnostic efficacy in the upper lobe, subsolid nodules and nodules ≥8 mm.

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Section: Discussionmentioning

confidence: 99%

The combination of CTCs and CEA can help guide the management of patients with SPNs suspected of being lung cancer

et al. 2020

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“…CTC enrichment and analysis. CTCs from mCRPC patient blood samples (20 ml) were enriched using the cell adhesion matrix (CAM) + FACS assay described previously (71). Briefly, blood from patients was incubated with RBC lysis buffer in a 50-ml conical tube for 5 minutes.…”

Section: Methodsmentioning

confidence: 99%

Targeting CD46 for both adenocarcinoma and neuroendocrine prostate cancer

Su¹,

Liu²,

Behrens³

et al. 2018

JCI Insight

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Although initially responsive to androgen signaling inhibitors (ASIs), metastatic castration-resistant prostate cancer (mCRPC) inevitably develops and is incurable. In addition to adenocarcinoma (adeno), neuroendocrine prostate cancer (NEPC) emerges to confer ASI resistance. We have previously combined laser capture microdissection and phage antibody display library selection on human cancer specimens and identified novel internalizing antibodies binding to tumor cells residing in their tissue microenvironment. We identified the target antigen for one of these antibodies as CD46, a multifunctional protein that is best known for negatively regulating the innate immune system. CD46 is overexpressed in primary tumor tissue and CRPC (localized and metastatic; adeno and NEPC), but expressed at low levels on normal tissues except for placental trophoblasts and prostate epithelium. Abiraterone- and enzalutamide-treated mCRPC cells upregulate cell surface CD46 expression. Genomic analysis showed that the CD46 gene is gained in 45% abiraterone-resistant mCRPC patients. We conjugated a tubulin inhibitor to our macropinocytosing anti-CD46 antibody and showed that the resulting antibody-drug conjugate (ADC) potently and selectively kills both adeno and NEPC cell lines in vitro (sub-nM EC50) but not normal cells. CD46 ADC regressed and eliminated an mCRPC cell line xenograft in vivo in both subcutaneous and intrafemoral models. Exploratory toxicology studies of the CD46 ADC in non-human primates demonstrated an acceptable safety profile. Thus, CD46 is an excellent target for antibody-based therapy development, which has potential to be applicable to both adenocarcinoma and neuroendocrine types of mCRPC that are resistant to current treatment.

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“…Another study using a novel IsoFlux™ System microfluidic collection device appeared to demonstrate increased sensitivity to capture CTCs compared with CellSearch, and next generation sequencing could be performed for a selected panel of genes [69]. Newer methodologies to isolate a larger number of CTCs continue to be studied, which may enhance the ability to more comprehensively perform molecular profiling in most patients [70–72]. One study simultaneously assessed 2 platforms - the ScreenCell Cyto platform which uses a size-selective enrichment method followed by central pathological review and the immunomagnetic Adna TestSelect kit to assess gene expression level of EPCAM and MUC1 by RT-PCR - in 3 cohorts of patients undergoing neoadjuvant therapy for MIBC, first line MVAC for metastatic disease and second line anti-TGF β therapy.…”

Section: Potential Circulating Biomarker Platformsmentioning

confidence: 99%

Circulating Biomarkers in Bladder Cancer

Nandagopal

Sonpavde

2016

BLC

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Bladder cancer is a molecularly heterogeneous disease characterized by multiple unmet needs in the realm of diagnosis, clinical staging, monitoring and therapy. There is an urgent need to develop precision medicine for advanced urothelial carcinoma. Given the difficulty of serial analyses of metastatic tumor tissue to identify resistance and new therapeutic targets, development of non-invasive monitoring using circulating molecular biomarkers is critically important. Although the development of circulating biomarkers for the management of bladder cancer is in its infancy and may currently suffer from lower sensitivity of detection, they have inherent advantages owing to non-invasiveness. Additionally, circulating molecular alterations may capture tumor heterogeneity without the sampling bias of tissue biopsy. This review describes the accumulating data to support further development of circulating biomarkers including circulating tumor cells, cell-free circulating tumor (ct)-DNA, RNA, micro-RNA and proteomics to improve the management of bladder cancer.

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An improved CTC isolation scheme for pairing with downstream genomics: Demonstrating clinical utility in metastatic prostate, lung and pancreatic cancer

Cited by 25 publications

References 57 publications

The combination of CTCs and CEA can help guide the management of patients with SPNs suspected of being lung cancer

The combination of CTCs and CEA can help guide the management of patients with SPNs suspected of being lung cancer

Targeting CD46 for both adenocarcinoma and neuroendocrine prostate cancer

Circulating Biomarkers in Bladder Cancer

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