Pingping Zhu and colleagues systematically described regulatory mechanisms and targeted strategies of CSCs in digestive system tumors

Digestive system tumors, containing colorectal tumor, liver tumor, esophageal tumor, gastric tumor, pancreatic tumor and cholangiocarcinoma, are characterized with high risks of drug resistance, recurrence and metastasis, cause huge medical and economic burdens to human society. Cancer stem cells (CSCs) are “seed cells” for tumor initiation, drug resistance, recurrence and metastasis. Therefore, a comprehensive understanding and intelligent targeting CSCs are expected to bring breakthroughs in the treatment of digestive system tumors.

There are four major sections in the review. Firstly, they described the characteristics of self-renewal, differentiation and tumorigenicity of CSCs in digestive system tumors, and focused on up to date understanding about the origin, heterogeneity and plasticity of CSCs. Secondly, the endogenous regulatory mechanisms of CSC were discussed in detail, including signaling pathways, metabolic pathways, transcription factors, epigenetic factors and non-coding RNAs. Thirdly, niche and systemic regulatory mechanisms of CSCs were summarized, including niche cells such as tumor non-stem cells, immune cells, endothelial cells, fibroblasts, neurons and fat cells, niche factors such as pathogenic bacteria, extracellular matrix, hypoxia, acid, inflammation factors, as well as distal organs, individual behavior and comorbidities. Finally, they reviewed the current tumor-targeting strategies via CSC elimination and niche remodeling, and listed the latest progress in basic research and clinical trial.

This paper highlights some previously neglected characteristics of CSCs. Firstly, they reviewed the new progresses in vivo characteristics (including self-renewal, differentiation, plasticity) of CSCs via new techniques such as lineage tracing, and in vivo cell-origin dissection of CSCs reveals the complicated transformation process from normal stem cells to CSCs. Secondly, they demonstrated the dynamic and feedback regulations between CSCs and their niche. CSCs reshape their niche during tumorigenesis and progression, and CSC niche further maintains stemness and identify of CSCs. The mutual interaction between CSCs and their niche enriches our understanding of cell plasticity and raises a challenge to study CSCs comprehensively and dynamically. Thirdly, they demonstrated the systemic regulation of CSCs, including remote tissues such as adipose tissue and brain, physiological/behavioral factors such as rhythm disorders and psychological pressure, and pathological factors such as complications, providing additional layers for understanding and targeting CSCs in digestive system tumors.

Altogether, Pingping Zhu and colleagues not only discussed in depth the characteristics, regulatory factors and targeted therapy of CSCs, but also raised the prospects and challenges of CSC targeting, providing important information for researchers in CSC, niche and targeting fields.

See more abluot the article from: https://doi.org/10.1002/mog2.70015.

Published in MedComm - Oncology