Inferring the Evolution and Progression of Small-Cell Lung Cancer by Single-Cell Sequencing of Circulating Tumor Cells

Su, Zhe; Wang, Zhijie; Ni, Xiaohui; Duan, Jianchun; Gao, Yan; Zhuo, Minglei; Li, Ruoyan; Zhao, Jun; Ma, Qi; Bai, Hua; Chen, Hengyu; Wang, Shuhang; Chen, Xixi; An, Tongtong; Wang, Yuyan; Tian, Yanhua; Yu, Jiangyong; Wang, Di; Xie, X. Sunney; Bai, Fan; Wang, Jie

doi:10.1158/1078-0432.ccr-18-3571

Cited by 65 publications

(62 citation statements)

References 34 publications

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“…In CTCs, genome-wide CNVs were found to be highly reproducible from cell to cell within the same individual and across different lung cancer patients with same pathological subtypes [43,45]. This is consistent with homogeneity found in CTCs from SCLC [42,46] and colorectal cancer patients [45].…”

Section: Ctc Heterogeneity and Clinical Impactsupporting

confidence: 71%

Single-Cell Analysis of Circulating Tumor Cells: Why Heterogeneity Matters

Lim

2019

Cancers

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Unlike bulk-cell analysis, single-cell approaches have the advantage of assessing cellular heterogeneity that governs key aspects of tumor biology. Yet, their applications to circulating tumor cells (CTCs) are relatively limited, due mainly to the technical challenges resulting from extreme rarity of CTCs. Nevertheless, recent advances in microfluidics and immunoaffinity enrichment technologies along with sequencing platforms have fueled studies aiming to enrich, isolate, and sequence whole genomes of CTCs with high fidelity across various malignancies. Here, we review recent single-cell CTC (scCTC) sequencing efforts, and the integrated workflows, that have successfully characterized patient-derived CTCs. We examine how these studies uncover DNA alterations occurring at multiple molecular levels ranging from point mutations to chromosomal rearrangements from a single CTC, and discuss their cellular heterogeneity and clinical consequences. Finally, we highlight emerging strategies to address key challenges currently limiting the translation of these findings to clinical practice.

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Section: Ctc Heterogeneity and Clinical Impactsupporting

confidence: 71%

Single-Cell Analysis of Circulating Tumor Cells: Why Heterogeneity Matters

Lim

2019

Cancers

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“…The expression characteristics of CTC may be higher than those of other cancer types. Su et al [ 52 ] performed whole genome sequencing detection of CTC in 10 patients with small-cell lung cancer who received standard chemotherapy regimens of etoposide + platinum (cisplatin, neda platinum or carboplatin). Amongst the 91 CTCs selected, the CNA spectra of patients’ CTC were found highly consistent, which also confirmed that CTC could be used as an ideal sample for clinical correlation analysis of patients with cancer.…”

Section: Single-cell Sequencing Of Ctc To Predict Drug Resistance In mentioning

confidence: 99%

Research and application of single-cell sequencing in tumor heterogeneity and drug resistance of circulating tumor cells

Dai

Xiang

et al. 2020

Biomark Res

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Malignant tumor is a largely harmful disease worldwide. The cure rate of malignant tumors increases with the continuous discovery of anti-tumor drugs and the optimisation of chemotherapy options. However, drug resistance of tumor cells remains a massive obstacle in the treatment of anti-tumor drugs. The heterogeneity of malignant tumors makes studying it further difficult for us. In recent years, using single-cell sequencing technology to study and analyse circulating tumor cells can avoid the interference of tumor heterogeneity and provide a new perspective for us to understand tumor drug resistance.

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“…With advances in next-generation sequencing (NGS) and single-cell sequencing (SCS) technologies, scientists can obtain the complete genome of a CTC and compare it with corresponding primary and metastatic tumours [113,120]. Molecular analysis of CTCs has predicted chemosensitive or refractory disease and subsequent patient outcomes [121].…”

Section: Advances In Biomarkersmentioning

confidence: 99%

“…Molecular analysis of CTCs has predicted chemosensitive or refractory disease and subsequent patient outcomes [121]. With specific focus on copy number aberrations (CNAs), Su et al showed utility of single cell sequencing of CTC with regards to survival, chemotherapy response, and heterogeneity by tracing allele specific CNAs in CTCs isolated at different timepoints of chemotherapy [120]. Phenotypic heterogeneity was also found with regards to expression of Bcl-2, CK, Vim, and M30 [120].…”

Section: Advances In Biomarkersmentioning

confidence: 99%

“…With specific focus on copy number aberrations (CNAs), Su et al showed utility of single cell sequencing of CTC with regards to survival, chemotherapy response, and heterogeneity by tracing allele specific CNAs in CTCs isolated at different timepoints of chemotherapy [120]. Phenotypic heterogeneity was also found with regards to expression of Bcl-2, CK, Vim, and M30 [120]. Implantation of CTCs into immunodeficient mice to generate CTC-derived explants may become a useful alternative to patient derived xenograft (PDX) models to effectively mirror the donor tumour.…”

Section: Advances In Biomarkersmentioning

confidence: 99%

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Technological and Therapeutic Advances in Advanced Small Cell Lung Cancer

Lum

Alamgeer

2019

Cancers

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Small cell lung cancer (SCLC) accounts for approximately 10–15% of all lung cancers. The prognosis is poor with median survival in the advanced stage remaining at around 12 months. Despite applying every known therapeutic approach, no major breakthrough has improved the overall survival in the last 30 years. Historically, experiments performed on conventional cell lines may have limitations of not accurately reflecting the complex biological and genomic heterogeneity of this disease. However, additional knowledge gained from recently developed genetically engineered mouse models (GEMMs) and patient derived xenografts (PDXs) have made encouraging inroads. Whole genome sequencing (WGS) data reveals a high mutational burden and a number of genetic alterations but low frequency of targetable mutations. Despite several failures, considerable therapeutic opportunities have recently emerged. Potentially promising therapies include those targeting DNA damage repair, stem cell/renewal and drug resistant mechanisms. Modest success has also been achieved with immune checkpoint inhibitors while therapeutic exploration of various other components of the immune system is underway. However, the complex heterogeneities reflect the need for accurate bio-markers to translate novel discoveries into clinical benefit. Additionally, the molecular mechanisms that differentiate chemo-sensitive from chemo-refractory disease remain unknown. Obtaining reliable tumour samples by utilising novel techniques such as endobronchial ultrasound guided needle aspiration or adopting to liquid biopsies are becoming popular. This review will focus on recent technological and therapeutic advancements to surmount this recalcitrant disease.

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Inferring the Evolution and Progression of Small-Cell Lung Cancer by Single-Cell Sequencing of Circulating Tumor Cells

Abstract: Purpose: Genomic analyses of small-cell lung cancer (SCLC) are limited by the availability of tumor specimens. This study aimed to investigate the suitability of single-cell sequencing of circulating tumor cells (CTC) as a method of inferring the evolution and progression of SCLCs.

Cited by 65 publications

References 34 publications

Single-Cell Analysis of Circulating Tumor Cells: Why Heterogeneity Matters

Single-Cell Analysis of Circulating Tumor Cells: Why Heterogeneity Matters

Research and application of single-cell sequencing in tumor heterogeneity and drug resistance of circulating tumor cells

Technological and Therapeutic Advances in Advanced Small Cell Lung Cancer

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