Research Progress on the Regulatory Mechanisms of the Liver Cancer Stem Cell Niche and Related Intervention Approaches

Liver cancer is a malignant tumor with relatively high incidence and mortality worldwide, and its high rates of recurrence and metastasis after treatment remain major challenges in clinical practice. Liver cancer stem cells(LCSCs) are considered to be a key cellular subpopulation driving the inititation, progression, drug resistance, recurrence, and metastasis of liver cancer. LCSCs do not exist independently; their stemness maintenance, self-renewal, and drug resistance properties are highly dependent on the specialized microenvironment in which they reside, namely the LCSC niche. This niche is composed of various stromal cells, including cancerassociated fibroblasts(CAFs), tumor-associated macrophages(TAMs), regulatory T cells(Tregs), and endothelial cells, as well as a complex extracellular matrix and abundant signaling molecules. This review systematically outlines the cellular composition of the LCSC niche and its key molecular regulatory networks, and further explores three tumor therapeutic strategies: targeting niche component cells, targeting molecular regulatory networks, and inducing differentiation of LCSCs. In addition, the review summarizes current technical and translational challenges faced by the field and provides an outlook on future research directions, aiming to offer a theoretical basis and insights for developing novel combination therapeutic strategies to eradicate LCSCs and improve the prognosis of patients with liver cancer.