Islam Farhadul, Gopalan Vinod, Smith Robert A, Lam Alfred K-Y
Cancer Molecular Pathology, School of Medicine and Menzies Health Institute Queensland, Griffith University, Gold Coast, Qld, Australia.
Cancer Molecular Pathology, School of Medicine and Menzies Health Institute Queensland, Griffith University, Gold Coast, Qld, Australia; Genomics Research Centre, Institute of Health and Biomedical Innovation, Faculty of Health, Queensland University of Technology, Brisbane, Qld, Australia.
Exp Cell Res. 2015 Jul 1;335(1):135-47. doi: 10.1016/j.yexcr.2015.04.018. Epub 2015 May 9.
Cancer stem cells (CSCs) are a subpopulation of cancer cells with many clinical implications in most cancer types. One important clinical implication of CSCs is their role in cancer metastases, as reflected by their ability to initiate and drive micro and macro-metastases. The other important contributing factor for CSCs in cancer management is their function in causing treatment resistance and recurrence in cancer via their activation of different signalling pathways such as Notch, Wnt/β-catenin, TGF-β, Hedgehog, PI3K/Akt/mTOR and JAK/STAT pathways. Thus, many different therapeutic approaches are being tested for prevention and treatment of cancer recurrence. These may include treatment strategies targeting altered genetic signalling pathways by blocking specific cell surface molecules, altering the cancer microenvironments that nurture cancer stem cells, inducing differentiation of CSCs, immunotherapy based on CSCs associated antigens, exploiting metabolites to kill CSCs, and designing small interfering RNA/DNA molecules that especially target CSCs. Because of the huge potential of these approaches to improve cancer management, it is important to identify and isolate cancer stem cells for precise study and application of prior the research on their role in cancer. Commonly used methodologies for detection and isolation of CSCs include functional, image-based, molecular, cytological sorting and filtration approaches, the use of different surface markers and xenotransplantation. Overall, given their significance in cancer biology, refining the isolation and targeting of CSCs will play an important role in future management of cancer.
癌症干细胞(CSCs)是癌细胞的一个亚群,在大多数癌症类型中具有许多临床意义。CSCs的一个重要临床意义在于它们在癌症转移中的作用,这体现在它们启动和驱动微转移和大转移的能力上。CSCs在癌症治疗中另一个重要的促成因素是它们通过激活不同的信号通路(如Notch、Wnt/β-连环蛋白、TGF-β、Hedgehog、PI3K/Akt/mTOR和JAK/STAT通路)导致癌症治疗耐药性和复发的功能。因此,许多不同的治疗方法正在被测试用于预防和治疗癌症复发。这些方法可能包括通过阻断特定细胞表面分子来靶向改变的基因信号通路的治疗策略、改变滋养癌症干细胞的癌症微环境、诱导CSCs分化、基于CSCs相关抗原的免疫疗法、利用代谢产物杀死CSCs以及设计特别靶向CSCs的小干扰RNA/DNA分子。由于这些方法在改善癌症治疗方面具有巨大潜力,在研究它们在癌症中的作用之前,识别和分离癌症干细胞以进行精确研究和应用非常重要。常用的检测和分离CSCs的方法包括功能、基于图像、分子、细胞分选和过滤方法、使用不同的表面标志物以及异种移植。总体而言,鉴于它们在癌症生物学中的重要性,完善CSCs的分离和靶向将在未来癌症治疗中发挥重要作用。