Guo Shanchun, Zheng Shilong, Liu Mingli, Wang Guangdi
RCMI Cancer Research Center and Department of Chemistry, Xavier University of Louisiana, New Orleans, LA 70125, USA.
Department of Biochemistry & Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Pharmaceutics. 2024 Aug 1;16(8):1024. doi: 10.3390/pharmaceutics16081024.
Cancer stem cells (CSCs) possess a significant ability to renew themselves, which gives them a strong capacity to form tumors and expand to encompass additional body areas. In addition, they possess inherent resistance to chemotherapy and radiation therapies used to treat many forms of cancer. Scientists have focused on investigating the signaling pathways that are highly linked to the ability of CSCs to renew themselves and maintain their stem cell properties. The pathways encompassed are Notch, Wnt/β-catenin, hedgehog, STAT3, NF-κB, PI-3K/Akt/mTOR, sirtuin, ALDH, MDM2, and ROS. Recent studies indicate that directing efforts towards CSC cells is essential in eradicating the overall cancer cell population and reducing the likelihood of tumor metastasis. As our comprehension of the mechanisms that stimulate CSC activity, growth, and resistance to chemotherapy advances, the discovery of therapeutic drugs specifically targeting CSCs, such as small-molecule compounds, holds the potential to revolutionize cancer therapy. This review article examines and analyzes the novel anti-CSC compounds that have demonstrated effective and selective targeting of pathways associated with the renewal and stemness of CSCs. We also discussed their special drug metabolism and absorption mechanisms. CSCs have been the subject of much study in cancer biology. As a possible treatment for malignancies, small-molecule drugs that target CSCs are gaining more and more attention. This article provides a comprehensive review of the current state of key small-molecule compounds, summarizes their recent developments, and anticipates the future discovery of even more potent and targeted compounds, opening up new avenues for cancer treatment.
癌症干细胞(CSCs)具有显著的自我更新能力,这赋予它们强大的形成肿瘤并扩散至身体其他部位的能力。此外,它们对用于治疗多种癌症的化疗和放疗具有内在抗性。科学家们专注于研究与癌症干细胞自我更新能力及维持其干细胞特性高度相关的信号通路。所涉及的通路包括Notch、Wnt/β-连环蛋白、刺猬蛋白、信号转导和转录激活因子3(STAT3)、核因子κB(NF-κB)、磷脂酰肌醇-3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(PI-3K/Akt/mTOR)、沉默调节蛋白、乙醛脱氢酶(ALDH)、小鼠双微体2(MDM2)和活性氧(ROS)。最近的研究表明,针对癌症干细胞的研究对于根除整个癌细胞群体和降低肿瘤转移的可能性至关重要。随着我们对刺激癌症干细胞活性、生长及化疗抗性机制的理解不断深入,发现专门靶向癌症干细胞的治疗药物,如小分子化合物,有望彻底改变癌症治疗方式。这篇综述文章研究并分析了新型抗癌症干细胞化合物,这些化合物已证明能有效且选择性地靶向与癌症干细胞更新和干性相关的通路。我们还讨论了它们特殊的药物代谢和吸收机制。癌症干细胞一直是癌症生物学领域众多研究的主题。作为一种可能的恶性肿瘤治疗方法,靶向癌症干细胞的小分子药物正受到越来越多的关注。本文全面综述了关键小分子化合物目前的研究状况,总结了它们的最新进展,并展望了未来发现更有效且靶向性更强的化合物,为癌症治疗开辟新途径。