State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
J Control Release. 2023 Aug;360:468-481. doi: 10.1016/j.jconrel.2023.06.036. Epub 2023 Jul 12.
Tumor angiogenesis and cancer stem cells (CSCs) are two major hallmarks of solid tumors. They have long received attention for their critical roles in tumor progression, metastasis and recurrence. Meanwhile, plenty of evidence indicates the close association between CSCs and tumor vasculature. CSCs are proven to promote tumor angiogenesis, and the highly vascularized tumor microenvironment further maintains CSCs growth in return, thereby forming a hard-breaking vicious circle to promote tumor development. Hence, though monotherapy targeting tumor vasculature or CSCs has been extensively studied over the past decades, the poor prognosis has been limiting the clinical application. This review summarizes the crosstalk between tumor vasculature and CSCs with emphasis on small-molecule compounds and the associated biological signaling pathways. We also highlight the importance of linking tumor vessels to CSCs to disrupt the CSCs-angiogenesis vicious circle. More precise treatment regimens targeting tumor vasculature and CSCs are expected to benefit future tumor treatment development.
肿瘤血管生成和癌症干细胞(CSCs)是实体瘤的两个主要标志。它们在肿瘤进展、转移和复发中的关键作用长期以来一直受到关注。同时,大量证据表明 CSCs 与肿瘤血管密切相关。CSCs 被证明可促进肿瘤血管生成,而高度血管化的肿瘤微环境反过来又维持 CSCs 的生长,从而形成促进肿瘤发展的恶性循环。因此,尽管过去几十年广泛研究了针对肿瘤血管或 CSCs 的单一疗法,但预后不佳限制了其临床应用。本综述总结了肿瘤血管与 CSCs 之间的串扰,重点介绍了小分子化合物及相关的生物学信号通路。我们还强调了将肿瘤血管与 CSCs 联系起来以破坏 CSCs-血管生成恶性循环的重要性。针对肿瘤血管和 CSCs 的更精确治疗方案有望有益于未来的肿瘤治疗发展。