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Emerging targets in pancreatic cancer: epithelial–mesenchymal transition and cancer stem cells

机译:胰腺癌的新兴靶标:上皮-间质转化和癌症干细胞

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摘要

Pancreatic ductal adenocarcinoma is one of the most aggressive solid malignancies and is characterized by poor response to current therapy and a dismal survival rate. Recent insights regarding the role of cancer stem cells (CSCs) and epithelial–mesenchymal transition (EMT) in tumorigenesis have brought further understanding to the field and have highlighted new therapeutic targets. CSCs are a distinct subset of cancer cells, with the ability to differentiate into other cell types and self-renew in order to fuel the maintenance of tumor amplification. Transition of a cancer cell from an EMT leads to increased migratory and invasive properties, and thus facilitates initiation of metastasis. EMT is regulated by a complex network of factors that includes cytokines, growth factors, aberrant signaling pathways, transcription factors, and the tumor microenvironment. There is emerging evidence that the EMT process may give rise to CSCs, or at least cells with stem cell-like properties. We review the key pathways involved in both of these processes, the biomarkers used to identify CSCs, and new therapeutic approaches targeting CSCs and EMT in pancreatic ductal adenocarcinoma.
机译:胰腺导管腺癌是最具侵略性的实体恶性肿瘤之一,其特点是对现有疗法反应差,生存率低。关于癌症干细胞(CSCs)和上皮间质转化(EMT)在肿瘤发生中的作用的最新见解为该领域带来了进一步的了解,并突出了新的治疗靶点。 CSC是癌细胞的一个独特子集,具有分化为其他细胞类型并自我更新的能力,以促进维持肿瘤扩增。癌细胞从EMT过渡导致迁移和侵袭特性增加,因此促进了转移的开始。 EMT由复杂的因素网络调节,这些因素包括细胞因子,生长因子,异常的信号传导途径,转录因子和肿瘤微环境。新兴证据表明,EMT过程可能会产生CSC,或者至少会产生具有干细胞样特性的细胞。我们回顾了涉及这两个过程的关键途径,用于鉴定CSC的生物标记物以及针对CSCs和EMT的胰腺导管腺癌的新治疗方法。

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