Most cited article - PubMed ID 25493031
Circulating tumor cells in pancreatic cancer patients: enrichment and cultivation
Pancreatic ductal adenocarcinoma represents a disease with increasing incidence. Its prognosis is the worst among all malignancies despite the aggressive combined multimodal treatment across all stages. In metastatic disease, median survival is approximatelly one year. The mainstay of treatment is chemotherapy (neo/adjuvant, palliative) and in selected subgroups of patients even radiotherapy. Nevertheless, nowadays there are very few prognostic and/or predictive biomarkers available that can be used to identify and better stratify patients based on risk to tailored treatment. Potentially, promising areas of research are circulating tumor cells and circulating tumor DNA, which can be easily obtained from peripheral blood - so called liquid biopsy. They may serve as a tool to assess response to applied treatment, and to detect the emergence of treatment-resistant clones or early disease relapse. Moreover, their study may allow identification of potentially tumor-specific alterations, which may serve as target structures for targeted (tailored) therapy. Alternatively, different prognostic indexes/scores calculated by analysis of selected parameters of blood and/or biochemistry can be used to better stratify patients based on risk and better predict prognosis. The aim of this mini-review is to provide a basic overview of the current state of the art in this area and its potential significance for clinical practice.
- Keywords
- Pancreatic carcinoma, biomarkers, circulating tumor DNA (ctDNA), circulating tumor cells (CTC), liquid biopsy, prognostic index/score, review,
- MeSH
- Circulating Tumor DNA * genetics MeSH
- Carcinoma, Pancreatic Ductal * diagnosis genetics therapy MeSH
- Humans MeSH
- Neoplasm Recurrence, Local MeSH
- Biomarkers, Tumor genetics MeSH
- Neoplastic Cells, Circulating * MeSH
- Pancreatic Neoplasms * diagnosis genetics therapy MeSH
- Prognosis MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Circulating Tumor DNA * MeSH
- Biomarkers, Tumor MeSH
BACKGROUND: In general, the presence of circulating tumor cells (CTCs) in peripheral blood (PB) is associated with a relative shorter overall survival in cancer patients. The clinical utility of CTC diagnostics is changing: from prognostic test to an assay predicting therapy response, enabling the right choice of therapy and monitoring the effect of administered therapy. We present two case reports of patients with suspicion of lung and pancreatic cancer, without obtainable preoperative biopsy for histological verification. The focus of the presented study was not to deliver a complete tumor tissue classification to the surgeon, but to answer the question if there is malignant disease or not. The results are based on CTC presence and characterization. MATERIALS AND METHODS: A size-based separation method for viable CTC enrichment from anticoagulated PB was used. The separated cells were cytomorphologically examined using vital fluorescent microscopy. Additionally, to confirm the epithelial origin of the cells on the separation membrane, CTC gene expression analysis was performed. RESULTS: CTCs were successfully enriched and cultured in vitro in both tested samples. The epithelial character of the captured cells was confirmed by quantitative-polymerase chain reaction (qPCR) analysis for a set of tumor-associated genes. CONCLUSION: Detection of cancer cells in PB (liquid biopsy) and their molecular characterization could significantly help complete the tumor diagnostic process in a time-efficient manner.
- Keywords
- CTC, MetaCell, liquid biopsy, lung cancer, pancreatic cancer, surgery,
- MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplastic Cells, Circulating metabolism pathology MeSH
- Lung Neoplasms blood genetics pathology MeSH
- Pancreatic Neoplasms blood genetics pathology MeSH
- Gene Expression Regulation, Neoplastic genetics MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
Circulating tumor cells (CTC) present in peripheral blood are assigned precursors of advanced tumor disease. Simplicity of blood withdrawal procedure adds practically an unlimited possibility of the CTC-monitoring and the advantages of the repeated biopsies over time. CTC got prognostic, predictive and diagnostic status with the technologic advance. Although the clinical utility of CTC has reached the high evidence, the significance of CTC testing was presented in the treatment strategy mostly with palliative intention. We report on the experiences with the CTC-testing in the CLIA-like laboratory working with the size-based CTC separation and in vitro culture. The data is presented in the form of case reports in patients with breast (BC), colorectal (CRC), prostate (PC) and lung cancer (NSCLC) to support the clinical utility of CTC during the neoadjuvant, adjuvant and palliative treatment. The presented findings support the evidence for liquid biopsy clinical implementation and enhance the ability of malignant disease monitoring and the treatment efficacy prediction.
- Keywords
- Circulating tumor cells, breast cancer, chemoresistance, colorectal cancer, non-small-cell lung cancer, prostate cancer,
- Publication type
- Journal Article MeSH