头颈部癌症是全球重大的健康问题，大多数病例发生在口腔部位。口腔鳞状细胞癌(OSCC)是口腔癌中最常见的类型，占所有病例的90%以上。与其他类型的癌症相比，OSCC具有更糟糕的预后，5年生存率为50%。此外，OSCC具有对化疗治疗的高抗药性，这可能部分解释了癌症干细胞(CSC)亚群的存在。CSC能够适应有害环境条件，并且对化疗和放疗治疗都具有高度抵抗性，从而促进肿瘤复发。本综述的目的是强调线粒体在口腔CSC中的作用，作为口腔癌治疗的潜在靶点。为此，我们回顾了口腔CSC中最验证的干细胞标志物、自噬、线粒体功能和能量代谢的一些基本方面。此外，我们将就为何能量代谢，特别是CSC中的氧化磷酸化，可能为新药物提供如此多样化的原始药理靶点进行讨论。最后，我们将描述一些能够干扰线粒体功能的药物，重点介绍那些旨在干扰电子传递链功能的药物，作为抗多药耐药的口腔CSC的新治疗策略。再利用已经获得临床批准的旧药物作为新抗肿瘤药物在癌症治疗中的应用也是修订的重点。版权所有 © 2023 由Elsevier Inc. 发布。

Head and neck cancer is a major health problem worldwide, with most cases arising in the oral cavity. Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, accounting for over 90% of all cases. Compared to other types of cancer, OSCC, has the worse prognosis, with a 5-year survival rate of 50%. Additionally, OSCC is characterized by a high rate of resistance to chemotherapy treatment, which may be partly explained by the presence of cancer stem cells (CSC) subpopulation. CSC can adapt to harmful environmental condition and are highly resistant to both chemotherapy and radiotherapy treatments, thus contributing to tumor relapse. The aim of this review is to highlight the role of mitochondria in oral CSC as a potential target for oral cancer treatment. For this purpose, we reviewed some fundamental aspects of the most validated protein markers of stemness, autophagy, the mitochondrial function and energy metabolism in oral CSC. Moreover, a discussion will be made on why energy metabolism, especially oxidative phosphorylation in CSC, may offer such a diverse source of original pharmacological target for new drugs. Finally, we will describe some drugs able to disturb mitochondrial function, with emphasis on those aimed to interrupt the electron transport chain function, as novel therapeutic strategies in multidrug-resistant oral CSC. The reutilization of old drugs approved for clinical use as new antineoplastics, in cancer treatment, is also matter of revision.Copyright © 2023. Published by Elsevier Inc.