Acharya Surendra Kumar, Shai Saptarsi, Choon Yee Fan, Gunardi Indrayadi, Hartanto Firstine Kelsi, Kadir Kathreena, Roychoudhury Ajoy, Amtha Rahmi, Vincent-Chong Vui King
Department of Oral Medicine, Radiology and Surgery, Faculty of Dentistry, Lincoln University College, Petaling Jaya 47301, Selangor, Malaysia.
Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA.
Biomedicines. 2024 Sep 16;12(9):2111. doi: 10.3390/biomedicines12092111.
Cancer stem cells (CSCs) represent a subpopulation of cancer cells that are believed to initiate and drive cancer progression. In animal models, xenotransplanted CSCs have demonstrated the ability to produce tumors. Since their initial isolation in blood cancers, CSCs have been identified in various solid human cancers, including oral squamous cell carcinoma (OSCC). In addition to their tumorigenic properties, dysregulated stem-cell-related signaling pathways-Wnt family member (Wnt), neurogenic locus notch homolog protein (Notch), and hedgehog-have been shown to endow CSCs with characteristics like self-renewal, phenotypic plasticity, and chemoresistance, contributing to recurrence and treatment failure. Consequently, CSCs have become targets for new therapeutic agents, with some currently in different phases of clinical trials. Notably, small molecule inhibitors of the hedgehog signaling pathway, such as vismodegib and glasdegib, have been approved for the treatment of basal cell carcinoma and acute myeloid leukemia, respectively. Other strategies for eradicating CSCs include natural compounds, nano-drug delivery systems, targeting mitochondria and the CSC microenvironment, autophagy, hyperthermia, and immunotherapy. Despite the extensive documentation of CSCs in OSCC since its first demonstration in head and neck (HN) SCC in 2007, none of these novel pharmacological approaches have yet entered clinical trials for OSCC patients. This narrative review summarizes the in vivo and in vitro evidence of CSCs and CSC-related signaling pathways in OSCC, highlighting their role in promoting chemoresistance and immunotherapy resistance. Additionally, it addresses methodological challenges and discusses future research directions to improve experimental systems and advance CSC studies.
癌症干细胞（CSCs）是癌细胞的一个亚群，被认为启动并推动癌症进展。在动物模型中，异种移植的癌症干细胞已证明具有产生肿瘤的能力。自首次在血液癌症中分离出癌症干细胞以来，已在包括口腔鳞状细胞癌（OSCC）在内的多种人类实体癌中发现了癌症干细胞。除了其致瘤特性外，失调的干细胞相关信号通路——Wnt家族成员（Wnt）、神经源性位点Notch同源蛋白（Notch）和刺猬信号通路——已被证明赋予癌症干细胞自我更新、表型可塑性和化疗耐药性等特征，导致复发和治疗失败。因此，癌症干细胞已成为新型治疗药物的靶点，其中一些目前正处于不同阶段的临床试验中。值得注意的是，刺猬信号通路的小分子抑制剂，如维莫德吉和格拉斯吉布，已分别被批准用于治疗基底细胞癌和急性髓系白血病。其他根除癌症干细胞的策略包括天然化合物、纳米药物递送系统、靶向线粒体和癌症干细胞微环境、自噬、热疗和免疫疗法。尽管自2007年首次在头颈部（HN）鳞状细胞癌中证明癌症干细胞以来，OSCC中已有大量关于癌症干细胞的文献记载，但这些新型药理学方法均未进入OSCC患者的临床试验。本叙述性综述总结了OSCC中癌症干细胞和癌症干细胞相关信号通路的体内和体外证据，强调了它们在促进化疗耐药性和免疫治疗耐药性中的作用。此外，它还解决了方法学挑战，并讨论了未来的研究方向，以改进实验系统并推进癌症干细胞研究。
