Correia Cristina, Weiskittel Taylor M, Ung Choong Yong, Villasboas Bisneto Jose C, Billadeau Daniel D, Kaufmann Scott H, Li Hu
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, United States.
Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, United States.
Front Cell Dev Biol. 2022 Mar 11;10:752326. doi: 10.3389/fcell.2022.752326. eCollection 2022.
Cancer stem cells (CSCs) represent a small fraction of the total cancer cell population, yet they are thought to drive disease propagation, therapy resistance and relapse. Like healthy stem cells, CSCs possess the ability to self-renew and differentiate. These stemness phenotypes of CSCs rely on multiple molecular cues, including signaling pathways (for example, WNT, Notch and Hedgehog), cell surface molecules that interact with cellular niche components, and microenvironmental interactions with immune cells. Despite the importance of understanding CSC biology, our knowledge of how neighboring immune and tumor cell populations collectively shape CSC stemness is incomplete. Here, we provide a systems biology perspective on the crucial roles of cellular population identification and dissection of cell regulatory states. By reviewing state-of-the-art single-cell technologies, we show how innovative systems-based analysis enables a deeper understanding of the stemness of the tumor niche and the influence of intratumoral cancer cell and immune cell compositions. We also summarize strategies for refining CSC systems biology, and the potential role of this approach in the development of improved anticancer treatments. Because CSCs are amenable to cellular transitions, we envision how systems pharmacology can become a major engine for discovery of novel targets and drug candidates that can modulate state transitions for tumor cell reprogramming. Our aim is to provide deeper insights into cancer stemness from a systems perspective. We believe this approach has great potential to guide the development of more effective personalized cancer therapies that can prevent CSC-mediated relapse.
癌症干细胞（CSCs）仅占癌症细胞总数的一小部分，但它们被认为是驱动疾病传播、治疗抗性和复发的原因。与健康干细胞一样，CSCs具有自我更新和分化的能力。CSCs的这些干性表型依赖于多种分子信号，包括信号通路（例如，WNT、Notch和Hedgehog）、与细胞龛位成分相互作用的细胞表面分子，以及与免疫细胞的微环境相互作用。尽管了解CSC生物学很重要，但我们对于邻近的免疫细胞和肿瘤细胞群体如何共同塑造CSC干性的认识仍不完整。在这里，我们从系统生物学的角度阐述了细胞群体识别和细胞调控状态剖析的关键作用。通过回顾最先进的单细胞技术，我们展示了基于创新系统的分析如何能够更深入地理解肿瘤龛位的干性以及肿瘤内癌细胞和免疫细胞组成的影响。我们还总结了完善CSC系统生物学的策略，以及这种方法在开发改进的抗癌治疗中的潜在作用。由于CSCs易于发生细胞转变，我们设想系统药理学如何能够成为发现新型靶点和候选药物的主要动力，这些靶点和药物可以调节状态转变以实现肿瘤细胞重编程。我们的目标是从系统角度更深入地洞察癌症干性。我们相信这种方法具有巨大潜力，可指导开发更有效的个性化癌症治疗方法，以预防CSC介导的复发。
