Autologous cell lines from circulating colon cancer cells captured from sequential liquid biopsies as model to study therapy-driven tumor changes

Soler, Alexandra; Cayrefourcq, Laure; Mazard, Thibault; Babayan, Anna; Lamy, Pierre‐Jean; Assou, Saïd; Assenat, Éric; Pantel, Klaus; Alix‐Panabières, Catherine

doi:10.1038/s41598-018-34365-z

Cited by 69 publications

(71 citation statements)

References 40 publications

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“…Nevertheless, our results are in line with those described by other authors, who found CD44v6 expression in CTC cultured lines and demonstrated the existence of patient-derived colorectal CTC that bear all the functional attributes of CSC [16,17]. Although these models are promising in drug-screening and resistance mechanism research, they are technically challenging, time-consuming and costly, thus not suitable for routine clinical practice.…”

Section: Discussionsupporting

confidence: 89%

Baseline CD44v6-positive circulating tumor cells to predict first-line treatment failure in patients with metastatic colorectal cancer

et al. 2020

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Section: Discussionsupporting

confidence: 89%

Baseline CD44v6-positive circulating tumor cells to predict first-line treatment failure in patients with metastatic colorectal cancer

et al. 2020

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“…Recent advances in CTC research have shown that CTCs are important clinical indicators for predicting metastatic progression and treatment efficacy . However, CTC investigation is hampered by their low number and heterogeneity.…”

Section: Discussionmentioning

confidence: 99%

“…SCID mice were co-inoculated with GFP-LOX cells and CDMWERVSRC, REMSDWRV or control vehicle DMEM medium progression and treatment efficacy. [8][9][10]19 However, CTC investigation is hampered by their low number and heterogeneity. Heterogeneity is commonly observed among various specimens from cancer patients including that of CTCs.…”

Section: Discussionmentioning

confidence: 99%

“…However, the efficiency in obtaining CTC cultures using these methods is low (<20%), except for a short‐term CTC cluster method showing efficiency of up to 60% . Importantly, CTC lines were developed using blood samples from a patient with metastatic colorectal cancer collected before and after chemotherapy and targeted therapy, and during cancer progression to show changes in mRNA and protein expression (eg, DEFA6, ABCB1, and GAL) over time of treatment . This paper shows that CTCs retain common genetic traits during therapy but may develop treatment‐resistant phenotypic characteristics over time.…”

Section: Introductionmentioning

confidence: 99%

“…6 Importantly, CTC lines were developed using blood samples from a patient with metastatic colorectal cancer collected before and after chemotherapy and targeted therapy, and during cancer progression to show changes in mRNA and protein expression (eg, DEFA6, ABCB1, and GAL) over time of treatment. 8 This paper shows that CTCs retain common genetic traits during therapy but may develop treatment-resistant phenotypic characteristics over time. Consistent with the observation that CTCs are heterogeneous in nature and that a specific CTC population isolated by a given method is a predictor for therapeutic response, SMAD4 expression of a CTC population called circulating tumor and invasive cells (CTICs) was able to predict response of pancreatic ductal adenocarcinoma.…”

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confidence: 99%

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The propensity of invasive circulating tumor cells (iCTCs) in metastatic progression and therapeutic responsiveness

et al. 2019

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Circulating tumor cells (CTCs) are important clinical indicators of metastatic progression and treatment efficacy. However, because of their low number and heterogeneity, reliable patient‐derived CTC models are not readily available. We report here the isolation and characterization of the invasive population of CTCs, iCTCs, from blood of 10 patients with epithelial ovarian cancer (EOC) and one pancreatic cancer patient based on the avidity of tumor cells toward an artificial collagen‐based adhesion matrix (CAM), in comparison with tumor progenitor (TP) cells isolated from tumor cell lines, tumors and ascites from EOC patients. CAM‐avid cells identified to be iCTCs were indistinguishable with TP cells using either functional CAM uptake or surface markers (seprase and CD44). In addition, iCTCs were characterized using peritoneal and spontaneous metastasis models in vivo to evaluate their metastatic propensity and therapeutic response. TP cells and iCTCs had a doubling time of about 34‐42 hours. TP cells were rare (<3.5%) in most patient‐derived specimens, however, iCTCs emigrated into blood, at a high frequency, 64.2% (n = 49). Approximately 500 patient‐derived iCTCs recapitulated formation of iCTCs in mouse blood and formed micrometastases in the liver and/or lung, a degree of metastatic spread equivalent to the inoculation of 5 × 10 5 bulk tumor cells isolated from ascites and tumors. iCTCs were shown to be novel therapeutic targets for blocking metastasis using the reduced formation of iCTCs and micrometastases by RNAi, peptides, and monoclonal antibodies against seprase.

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Anterior Approach vs Conventional Hepatectomy for Resection of Colorectal Liver Metastasis

et al. 2021

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IMPORTANCETumor relapse after partial hepatectomy for colorectal liver metastasis (CRLM) remains an unsolved issue. Intraoperative manipulation of the liver during conventional hepatectomy might enhance hematogenous tumor cell spread. The anterior approach is an alternative approach that may reduce intraoperative tumor cell dissemination.OBJECTIVE To determine the efficacy and safety of the anterior approach compared with conventional hepatectomy in patients undergoing resection for CRLM. DESIGN, SETTING, AND PARTICIPANTSThis randomized clinical study evaluated the efficacy and safety of the anterior approach compared with conventional hepatectomy in adult patients with CRLM who were scheduled for hepatectomy from February 1, 2003, to March 31, 2012, at a tertiary-care hospital. A total of 80 patients with CRLM were randomized to the anterior approach and conventional hepatectomy groups in a 1:1 ratio. Bone marrow and blood samples were analyzed for disseminated tumor cells and circulating tumor cells (CTC) using cytokeratin 20 reverse transcriptase-polymerase chain reaction analysis. Data were analyzed from April 1 to December 1, 2018, using intention to treat.INTERVENTIONS Anterior approach vs conventional hepatectomy. MAIN OUTCOMES AND MEASURESThe primary end point was intraoperative CTC detection in central blood samples after liver resection. Secondary end points included postoperative morbidity, mortality, and long-term survival. RESULTS Among the 80 patients included in the analysis (48 men [60%]; mean [SD] age, 61 [10] years), baseline characteristics, including preoperative CTC detection, were comparable between both groups. There was no statistically significant difference in intraoperative CTC detection between patients in the conventional hepatectomy (5 of 21 [24%]) and anterior approach (6 of 22 [27%]) groups (P > .99). Except for a longer operating time in the anterior approach group (mean [SD], 171 [53] vs 221 [53] minutes; P < .001), there were no significant differences in intraoperative and postoperative outcomes between both study groups. Although detection of CTC was associated with poor overall (median, 46 [95% CI,(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52) vs 81 [95% CI, 54-107] months; P = .03) and disease-free (median, 40 [95% CI,(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46) vs 60 [95% CI, 46-74] months; P = .04) survival, there was no significant difference in overall (median, 73 [95% CI, vs 55 [95% CI, 35-75] months; P = .43) and disease-free (median, 48 [95% CI,(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56) vs 40 [95% CI, 28-52] months; P = .88) survival between the conventional hepatectomy and anterior approach groups. Also, there was no significant difference in patterns of recurrence between both groups.CONCLUSIONS AND RELEVANCE This randomized clinical trial found that the anterior approach was not superior to conventional hepatectomy in reducing intraoperative tumor cell dissemination in patients undergoing resection of CRLM.

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Autologous cell lines from circulating colon cancer cells captured from sequential liquid biopsies as model to study therapy-driven tumor changes

Cited by 69 publications

References 40 publications

Baseline CD44v6-positive circulating tumor cells to predict first-line treatment failure in patients with metastatic colorectal cancer

Baseline CD44v6-positive circulating tumor cells to predict first-line treatment failure in patients with metastatic colorectal cancer

The propensity of invasive circulating tumor cells (iCTCs) in metastatic progression and therapeutic responsiveness

Anterior Approach vs Conventional Hepatectomy for Resection of Colorectal Liver Metastasis

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