Mesenchymal Characteristics and Predictive Biomarkers on Circulating Tumor Cells for Therapeutic Strategy
Abstract
:Simple Summary
Abstract
1. Introduction
2. The Significance of EMT in CTCs as Prognostic and Predictive Biomarkers
2.1. The Early Occurrence of EMT in CTCs
2.2. The Metastatic Ability of CTCs and CTC Clusters with a Mesenchymal Phenotype
3. Cancer Stem Cells (CSCs) with a Mesenchymal Phenotype
4. The Concordance between the Characteristics of CTCs and Primary Tumors
5. The Potential Markers on CTCs for Precision Medicine
5.1. The Analysis of Molecular Target Expression in CTCs as a Predictive Biomarker for Treatment Response
5.2. The Analysis of Oncogenic Driver Mutation in CTCs as a Predictive Biomarker for Treatment Response
5.3. The Immunophenotype Analysis of CTCs as Predictive Biomarkers for Immune Checkpoint Therapy Response
5.4. The Combination Analysis of EMT and Predictive Markers for Treatment Decision-Making
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Cancer Type | Molecular Marker on CTC | Detection Method | Significance as Biomarker | Positivity of Total Pts | Ref. |
---|---|---|---|---|---|
Advanced NSCLC | VIM | CellSearch® | Increasing in the EGFR-mutated subgroup | 20.80% | [68] |
Gastric cancer | VIM | Cyttel method | Immune evasion capacity of CTCs | 75.86% | [69] |
Gastric cancer | CSV/PD-L1 | CSV magnetic positive selection | Short survival duration and poor therapeutic response | 71% | [46] |
Lung cancer | VIM | Vimentin-iFISH | Shorter PFS | 19.70% | [70] |
Gastric cancer | CK+/CD44+ | Flow cytometry sorting | Shortened survival | 10% | [71] |
NSCLC | VIM/N-Cadherin/PD-L1 | Immunofluorescent staining | Poorer survival after curative surgery | 86.70% | [72] |
NSCLC | VIM/Twist | CanPatrol™ | Predictor of metastasis | 80.00% | [73] |
mBC | ALDH1/TWIST1 | Immunofluorescent staining | Chemoresistance, lung metastases, and decreased PFS | 27.70% | [22] |
CRPC | EpCAMlow-expression | CellSearch® | Shorter OS in ≥5 EpCAMhigh-expression CTC | 28.00% | [74] |
mBC | EpCAMlow-expression | CellSearch® | Shorter OS in ≥5 EpCAMhigh-expression CTC | 36% | [74] |
Colorectal cancer | LGR5+ | CanPatrol™ | Metastasis | 86.40% | [75] |
mBC (triple negative subtype) | VIM | Microfluidic Chip device | Shorter PFS | 100% | [51] |
Esophageal squamous cell carcinoma | VIM/Twist | CanPatrol™ | Staging | 32.60% | [76] |
Hepatocellular carcinoma | VIM/Twist | CanPatrol™ | Shortened postoperative disease-free survival | 38.79% | [75] |
Breast cancer | TUB/VIM/GLU | ISET | Metastases | 8.24% (VIM) | [77] |
Hepatocellular carcinoma | VIM/Twist | CanPatrol™ | Metastasis | 90.18% | [78] |
Colorectal cancer | AKT2/SNAIL1 | CanPatrol™ | Staging and metastasis | 56.90% | [79] |
Colorectal cancer | VIM | CanPatrol™ | Metastasis | 42.06% | [80] |
Hepatocellular carcinoma | VIM/Twist | CanPatrol™ | Shortened postoperative disease-free survival | 69.20% | [81] |
Prostate cancer | CK/VIM | Parsortix system | Tumor aggressiveness and poorer survival | 73% | [59] |
NSCLC | VIM | TelomeScan® | Shorter PFS | 46% | [23] |
Ovarian cancer | PI3Kα/Akt-2/Twist | AdnaTest OvarianCancer and EMT-1 | Suggested therapeutic resistance | 30% | [82] |
mBC | VIM/Twist | CanPatrol™ | Increasing in the negative hormone receptor subgroup | 93% | [83] |
mCRPC | VIM | CellSearch® | Shorter OS | 32.30% | [84] |
Cancer Type | Molecular Marker on CTC | Detection Method | Clinical Significance as Biomarker | Positivity of Total Pts | Ref. |
---|---|---|---|---|---|
Gastric cancer | CK+/CD44+ | Flow cytometry sorting | Shortened survival | 10% | [71] |
NSCLC | CD133 | Immunofluorescent staining | Shortened survival | 84% | [116] |
CRPC | CD133 | CellSearch® | Metastases | 82% | [117] |
Breast cancer | ALDH1 | Immunomagnetic cell selection | Recurrence and survival | 14% | [118] |
NSCLC | ALDH1 | RT-PCR following immunomagnetic cell selection | Progressive metastases | 25% | [120] |
mBC | ALDH1+/VIM+/fibronectin+ | Immunomagnetic cell selection | Metastases | 34% | [121] |
mBC | ALDH1/nuclear Twist | Immunofluorescent staining | Disease progression | 76% | [92] |
mBC | EMT markers (TWIST, Akt2, PI3K) and/or ALDH1 | Immunomagnetic cell selection | Therapy resistant | 38% | [122] |
Breast cancer | CD44+/CD24+ or low-expression | Immunofluorescent staining | Metastases | 23% | [123] |
Cancer Type | Molecular Marker on CTC | Detection Method | Clinical Significance as Biomarker | Positivity of Total Pts | Ref. |
---|---|---|---|---|---|
mCRPC | Nuclear-localized AR-V7 | Immunofluorescent staining | Therapeutic response of taxane | 22% | [176] |
Metastatic melanoma | PD-L1 | Multiparametric flow cytometry | Therapeutic response of pembrolizumab and longer PFS | 64% | [174] |
SCLC | DLL3+/CD45 | CellSearch® | Therapeutic response of etoposide/platinum and decreased PFS | 74.10% | [177] |
Rectal cancer | TYMS/RAD23B | ISET® | Predict resistance of neoadjuvant chemoradiotherapy | 100% (TYMS mRNA)/75% (RAD protein) | [178] |
NSCLC | PD-L1 | CellSearch® | Resistance to PD-1/PD-L1 blockade therapies | 47% | [170] |
Metastatic thyroid cancer | EpCAM-/CD45-/DAPI+/CEP8 | Aneuploidy | Poor response to 131I treatment and worse prognosis | 86.11% | [179] |
Advanced gastrointestinal tumor | PD-L1 | Immunofluorescent staining | Therapeutic response of PD-1/PD-L1 blockade therapies | 74% | [175] |
mBC | Topoisomerase 1 | ApoStream (enrich for CTCs) | Therapeutic response of topoisomerase 1 inhibitor etirinotecan pegol | 52% | [151] |
Advanced NSCLC | CEA/hTERT | CTC chip | Therapeutic response of nivolumab, PD-1 inhibitor | Only selected patients | [180] |
Advanced NSCLC | PD-L1 | ISET | Poor response to nivolumab, PD-1 inhibitor and shorter PFS | 83% | [172] |
mCRPC | Synaptophysin | CellSearch® | Resistance to AR-targeted therapies, abiraterone, and enzalutamide | Only selected patients | [150] |
SCLC | Bcl-2+ | Immunofluorescent staining | Prognostic and treatment efficacy | 72.70% | [152] |
mCRPC | AR splice variants | CellSearch® | Therapeutic response of taxane | 67%: AR-V7+, 78%: ARv567es+ | [161] |
mCRPC | AR splice variants | Flow cytometry | Therapeutic response of AR-targeted therapies, abiraterone, and enzalutamide | 26.5%: CTC cluster(+)/AR-V7(+) | [159] |
mCRPC | AR nuclear localization (%ARNL) | CellSearch® | Suggested resistance to taxane with increasing PSA | Only selected patients | [162] |
Advanced NSCLC with ALK rearrangement | ALK-CNG | ISET | Therapeutic response of ALK inhibitor, crizotinib, by decreasing CTC of ALK-CNG | 100% | [156] |
mCRPC | AR splice variants | EpCAM-based Prostate Cancer Select kit | Therapeutic response of AR-targeted therapies, abiraterone. and enzalutamide | 17.8%: AR-V7+ | [160] |
mBC | PIK3CA mutations | CellSearch® | Resistance to anti-HER2 therapy | 36.40% | [181] |
mBC | HER2 | CellSearch® | Therapeutic response of anti-HER2 therapy | 37.9 | [147] |
mCRPC | Nuclear-localized AR-V7 | Immunofluorescent staining | Resistance to AR inhibitors | 18% | [182] |
Advanced NSCLC | PD-L1 | CellSearch® | Resistance to nivolumab, PD-1 inhibitor | 93% | [183] |
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Okabe, T.; Togo, S.; Fujimoto, Y.; Watanabe, J.; Sumiyoshi, I.; Orimo, A.; Takahashi, K. Mesenchymal Characteristics and Predictive Biomarkers on Circulating Tumor Cells for Therapeutic Strategy. Cancers 2020, 12, 3588. https://doi.org/10.3390/cancers12123588
Okabe T, Togo S, Fujimoto Y, Watanabe J, Sumiyoshi I, Orimo A, Takahashi K. Mesenchymal Characteristics and Predictive Biomarkers on Circulating Tumor Cells for Therapeutic Strategy. Cancers. 2020; 12(12):3588. https://doi.org/10.3390/cancers12123588
Chicago/Turabian StyleOkabe, Takahiro, Shinsaku Togo, Yuichi Fujimoto, Junko Watanabe, Issei Sumiyoshi, Akira Orimo, and Kazuhisa Takahashi. 2020. "Mesenchymal Characteristics and Predictive Biomarkers on Circulating Tumor Cells for Therapeutic Strategy" Cancers 12, no. 12: 3588. https://doi.org/10.3390/cancers12123588