Microenvironmental Regulation of Colorectal Cancer Stemness: Technological Advances, Molecular Basis, and Therapeutic Targets

Cancer Heterogeneity and Plasticity 2025;2(2):0011 | https://doi.org/10.47248/chp2502020011

Review Open Access

Microenvironmental Regulation of Colorectal Cancer Stemness: Technological Advances, Molecular Basis, and Therapeutic Targets

Hui Zhao ^1,† , Qilin Li ^2,† , Jichao Qin ³

1. The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, 430074, China
2. Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
3. Department of Gastrointestinal Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China

† These authors contributed equally to this work, and they are considered as co-first authors.

Correspondence: Jichao Qin

Academic Editor(s): Dean G. Tang

Received: Nov 28, 2024 | Accepted: Jun 18, 2025 | Published: Jun 26, 2025

Cite this article: Zhao H, Li Q, Qin J. Microenvironmental Regulation of Colorectal Cancer Stemness: Technological Advances, Molecular Basis, and Therapeutic Targets. Cancer Heterog Plast. 2025;2(2):0011. https://doi.org/10.47248/chp2502020011

Abstract

Stem cell plasticity is crucial for rapidly proliferating tissues, such as the intestine, to cope with microenvironmental stress and maintain homeostasis. This framework may be employed by cancer stem cells (CSCs) to interact with the tumor microenvironment (TME) and give rise to drug resistance, tumor recurrence, and metastasis. Here, we consider colorectal cancer (CRC) as an example to review the technological and conceptual advances in microenvironmental regulation of cancer stemness. Some unique features of CRC, including reprogramming of stromal cells, bacterial niche alteration, and metabolic interplay, were summarized to illustrate how the TME affects the plasticity of CSCs. The key pathways and molecular mechanisms involved in metastasis and drug resistance are reviewed to obtain a deeper understanding of how CSCs may be manipulated for better outcomes in CRC treatment. These findings advance our knowledge of tumor heterogeneity and may provide insights into the development of novel therapeutic strategies.

Keywords

Colorectal cancer, tumor microenvironment, cancer stem cells, intestinal stem cells, stem cell plasticity

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