Uncovering Pharmacological Opportunities for Cancer Stem Cells—A Systems Biology View

Frontiers in Cell and Developmental Biology

Hu Li²  Choong Yong Ung²  Cristina Correia²  Taylor M Weiskittel²  Jose C Villasboas Bisneto³  Daniel D Billadeau⁴  Scott H Kaufmann⁴ 

[1] Department of Immunology, Mayo Clinic, Rochester, MN, United States;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;Division of Oncology Research, Mayo Clinic, Rochester, MN, United States;

关键词: cancer stem cells;    cellular niche;    tumor microenvironment;    systems biology;    immunotherapy;    drug resistance;   

DOI  :  10.3389/fcell.2022.752326

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown