Circulating tumor cells in the diagnosis and management of pancreatic cancer.

Circulating tumor cells in the diagnosis and management of pancreatic cancer.
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DOI:
10.1016/j.bbcan.2012.05.007
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发表时间:
2012-12
影响因子:
11.2
通讯作者:
Li, Min
Li, Min
中科院分区:
医学2区
文献类型:
--
作者:
Cen, Putao;Ni, Xiaoling;Yang, Jingxuan;Graham, David Y.;Li, Min

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胰腺癌通常对化疗和放射治疗有抵抗力,而且容易发生远处转移。循环肿瘤细胞(CTCs)是从原发和转移部位扩散的肿瘤细胞,可以从外周血中分离出来。CTC可克服现有肿瘤标志物CA19-9的局限性。作为“实时活组织检查”的替代品,CTC允许对肿瘤的生物学活性进行经常性的评估。我们综述了目前CTCs的提取和表征方法,包括基于抗体的免疫学检测、基于PCR的检测以及基于CTCs的物理或生物学特性的新技术。CTCs还提供了一种可接近的联系,与上皮间充质转化、肿瘤干细胞标记物的存在以及肿瘤中正在进行的克隆性突变和表观遗传学变化有关。我们还探讨了CTC图谱在胰腺癌的诊断、新辅助和辅助治疗的选择、复发疾病的检测、药效学生物标志物的检测以及基因治疗和免疫治疗中的应用潜力。正在进行的CTC鉴定不仅有可能代表从原发胰腺肿瘤和每个转移部位脱落的所有细胞,而且还允许在临床过程中的多个时间点进行动态采样,以确定CTC亚群和驱动转移和化疗耐药的特定分子。我们预测,CTC基因分型和表型分型将在个性化治疗、识别新的治疗靶点以及监测疾病的病程和状态方面发挥越来越大的作用。
Pancreatic cancers are typically resistant to chemo and radiation therapy and are predisposed to distant metastases. Circulating tumor cells (CTCs) are tumor cells disseminated from primary and metastatic sites and can be isolated from peripheral blood. CTC may overcome the limitation of the current available tumor markers, CA19-9. As a surrogate for ‘real-time biopsy’, CTCs allow recurrent assessment of a tumor’s biological activity. We review the current methodologies for CTCs extraction and characterization including antibody-based immunological assays, PCR-based assays, and novel technologies based on the physical or biological characteristics of CTCs. CTCs also provide an accessible link to the existence of epithelial to mesenchymal transition, tumor stem cell markers, and ongoing clonal mutations and epigenetic changes in the tumor. We also explore the potential of using CTC profiling in diagnosis, selection of neoadjuvant and adjuvant therapy, detection of recurrent disease, examination of pharmacodynamic biomarkers, as well as in gene therapy and immunotherapy for pancreatic cancer. Ongoing CTC characterization not only has the potential to represent all cells shed from primary pancreatic tumor and each metastatic site, but also allows dynamic sampling at multiple time points during the clinical course to identify the subpopulations of CTCs and the specific molecules driving metastasis and chemo resistance. We predict that CTC genotyping and phenotyping will play an increasing role in personalized therapy and in identification of novel therapeutic targets as well as monitoring the course and status of the disease.
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