Table 2 Clinical applications of CTCs in recent three years (from 2020 to 2022)
From: Detection of circulating tumor cells: opportunities and challenges
Cancer Type | CTCs Utility | Detection Methods | Molecular Characteristic | Main Findings/Purposes | Trial Identifier | Reference |
|---|---|---|---|---|---|---|
breast cancer | prognostic value | CellSearch® system | PI3KCA, ESR1 | the detection of 5 cells/7.5 mL of blood is the best cutoff point to stratify the patients’ prognosis | NA | [133] |
prognostic value; recurrence monitoring | an epithelial cell adhesion molecule–based, positive-selection microfluidic device | NA | the presence of circulating tumor DNA and circulating tumor cells after NAC in patients with early-stage TNBC was associated with significantly inferior distant DFS, DFS, and OS | NCT02101385 | [134] | |
therapeutic monitoring | CellSearch® system | NA | a 50% reduction in baseline apoptotic CTC count represents the optimal cut-off to differentiate between therapy response and disease progression | NA | [135] | |
prognostic value | CellSearch® system | HER2, CK | CTC heterogeneity in the blood of patients is inversely associated with OS. | NA | [136] | |
prognostic value; guiding therapy | CellSearch® system | HER2 | first-line HER2-targeted therapy of mBC seems to reduce CTC levels greater than endocrine or chemotherapy; anti-HER2 therapy seems to be associated with lower overall CTC levels. | NA | [44] | |
guiding therapy | CellSearch® system | HER2 | HER2 + CTCs ≥2 associated with shorter survival and higher risk for disease progression (HR 2.16) | NA | [137] | |
guiding therapy | CellSearch® system | PD-L1 | CTC and platelet PD-L1 expression could predict which patients should receive immune checkpoint inhibition and as a pharmacodynamics biomarker during treatment | NA | [138] | |
prognostic value | CellSearch® system | NA | mortality is on the number of CTC/7.5 mL WB in patients with mBC starting first-line chemotherapy | NCT00382018 | [139] | |
prognostic value | density-based isolation | TWIST1, CD24, CD44, and ALDH1 | TWIST1 in EpCAM+ cells had a significant lower DFS and OS | NA | [140] | |
prognostic value; therapeutic monitoring | CellSearch® system | NA | the addition of bevacizumab was associated with a PFS benefit regardless of CTC count, but an OS benefit was only observed in CTC-positive patients | NCT00601900 | [141] | |
prognostic value | GILUPI CellCollector | NA | evaluate the predictive value of CTC in NAC among locally advanced breast cancer patients. | NCT03732339 | No Results Posted | |
lung cancer | diagnostic value | ISET® | NA | the ISET Rarecells test used in this study had too low a sensitivity to be used as a reliable lung cancer screening tool for patients at high-risk | NCT02500693 | [142] |
prognostic value | EpCAM-independent | NA | the high number of CTC predicted adverse prognosis | NA | [143] | |
prognostic value | CytoploRare Kit | NA | preoperative CTC concentration is an independent and sensitive biomarker of prognosis in patients with NSCLC | NA | [144] | |
prognostic value | Microsieve membrane filter device | NA | evaluates the use of ctDNA and CTCs in predicting disease activity and drug response in lung cancer patients | NCT04254497 | No Results Posted | |
guiding therapy; therapeutic monitoring | ISET® | ALK | detection by FISH analysis and prevalence of escaping mutations in circulating tumor cells for the non-invasive management of lung cancer patients | NCT02372448 | No Results Posted | |
gastric cancer | prognostic value; guiding therapy | CellSearch® system | HER2 | HER2-expression on CTCs was an independent prognostic factor for both OS and PFS; the potential clinical utility of trastuzumab combined chemotherapy in patients with HER2-positive CTCs even if they are histologically HER2-negative | NA | [145] |
prognostic value | Ficoll | FGFR2 | patients with FGFR2-positive CTCs (≥5 cells/10 mL blood) had significantly worse RFS | NA | [146] | |
prognostic value | Ficoll | CEA | the number of EpCAM - /CEA + cells was higher in patients with stage II–IV than in patients with stage I; a lower number of CTCs indicated a higher 3-year RFS. | NA | [147] | |
therapy monitoring | CTCBIOPSY | NA | compare both short-term and long-term treatment effect of laparoscopic vs. open approach on progressive gastric and rectal cancer, based on circulating tumor cell (CTC) test results and DFS | NCT02955173 | No Results Posted | |
colorectal cancer | prognostic value | CellSearch® system | NA | elevated bCTCs and RASmut were associated with clinicopathologic features known to be associated with poor prognosis | NCT01640405NCT01640444 | [148] |
prognostic value | Density gradient isolation | CEACAM5 | using CEACAM5 as a dynamic poor prognostic CTC biomarker in patients with mCRC; MSI-High was identified as an unfavorable prognostic factor for tumors in patients with mCRC | NA | [149] | |
therapy monitoring | EPISPOT | NA | a prospective study of a cohort of patients with metastatic colorectal cancer was conducted to demonstrate the predictive value of CTC counts for treatment response. | NCT01596790 | No Results Posted | |
pancreatic cancer | guiding therapy; prognostic value | CellSearch® system | NA | patients with positive CTC (≥1) preoperatively had a poor prognosis despite successful tumor resection, a finding with high specificity. | NA | [150] |
hepatocellular Carcinoma | prognostic value | CellSearch® system | NA | CTC count ≥3 was associated with a higher risk of postoperative extrahepatic metastases; | NA | [151] |
prognostic value | CanPatrol | Nanog | the numbers of EpCAM mRNA+ CTCs and Nanog mRNA+ CTCs were strongly correlated with postoperative HCC recurrence | NA | [152] | |
prognostic value | CellSearch® system | NA | elucidate the association between the levels of CTC/CTC clusters and patients’ disease during the perioperative period; explore the molecular basis of CTC production in hepatocellular carcinoma. | NCT05297955 | No Results Posted | |
renal cell carcinoma | prognostic value | CellSearch® system | NA | the presence of ≥3 CTCs at baseline is associated with a significantly shorter PFS and OS in patients with mRCC | NA | [153] |
prognostic value | CanPatrol-ITMCTCs | NA | no differences in the OS and DFS between the different numbers of CTCs | NA | [154] | |
prostate cancer | guiding therapy | Streck tubes | AR-V7 | patients with detectable nuclear-localized AR-V7 in CTCs had superior survival with taxanes over ARSIs | NA | [155] |
prognostic value | VERSA | NA | a transcriptional profile detectable in CTCs can serve as an independent prognostic marker beyond AR-V7 in patients with mPC CTC can be used to identify the emergence of multiple ARSI resistance mechanisms. | NCT01942837 NCT02025010 | [156] | |
prognostic value | AdnaTest® | AR; AR-V7 | detection of AR-V7 in CTCs is independently associated with shorter PFS and OS with abiraterone or enzalutamide; men with AR-V7-positive disease experience clinical benefits from taxane chemotherapy | NA | [157] | |
prognostic value | Epic Sciences | AR | chromosomal instability of CTCs was associated with poor OS in patients treated with AR signaling inhibitors and taxanes. | NA | [158] | |
prognostic value | CellSearch® system | NA | low CTC detection rate in patients with locally advanced high-risk prostate cancer; the conversion of CTCs was significantly associated with stages T3 (P = 0.044) and N1 (P = 0.002); detection of CTCs was not significantly associated with overall survival (P > 0.40) | NCT01800058 | [159] | |
bladder Cancer | prognostic value | Telomerase-based technique | NA | detect tCTC levels in bladder cancer patients in different cohorts; clarify how tCTC levels vary with the natural history of bladder cancer; observe whether tCTCs provide new information. | NCT02246738 | No Results Posted |
gestational choriocarcinoma | guiding therapy | NanoVelcro system | NA | patients with ≥4 CTCs were more likely to develop chemoresistance than those with < 4 CTCs (P < 0.001) | NA | [127] |
gynaecological malignancy | prognostic value | CellSearch® system | NA | patients with ≥ 1 CTC at baseline had significantly shorter OS and PFS than CTC-negative patients | NA | [160] |