Xie Longlong, Zhou Tiansheng, Xie Yujun, Bode Ann M, Cao Ya
Hunan Children's Hospital, The Pediatric Academy of University of South China, Changsha, China.
Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Department of Radiology, Xiangya Hospital, Central South University, Changsha, China.
Front Oncol. 2021 Nov 18;11:769036. doi: 10.3389/fonc.2021.769036. eCollection 2021.
The emergence, in recent decades, of an entirely new area of "Mitochondrial dynamics", which consists principally of fission and fusion, reflects the recognition that mitochondria play a significant role in human tumorigenesis and response to therapeutics. Proteins that determine mitochondrial dynamics are referred to as "shaping proteins". Marked heterogeneity has been observed in the response of tumor cells to chemotherapy, which is associated with imbalances in mitochondrial dynamics and function leading to adaptive and acquired resistance to chemotherapeutic agents. Therefore, targeting mitochondria-shaping proteins may prove to be a promising approach to treat chemotherapy resistant cancers. In this review, we summarize the alterations of mitochondrial dynamics in chemotherapeutic processing and the antitumor mechanisms by which chemotherapy drugs synergize with mitochondria-shaping proteins. These might shed light on new biomarkers for better prediction of cancer chemosensitivity and contribute to the exploitation of potent therapeutic strategies for the clinical treatment of cancers.
近几十年来,一个全新的“线粒体动力学”领域出现了,其主要包括裂变和融合,这反映出人们认识到线粒体在人类肿瘤发生和对治疗的反应中起着重要作用。决定线粒体动力学的蛋白质被称为“塑形蛋白”。已观察到肿瘤细胞对化疗的反应存在显著异质性,这与线粒体动力学和功能的失衡有关,导致对化疗药物产生适应性和获得性耐药。因此,靶向线粒体塑形蛋白可能是治疗化疗耐药癌症的一种有前景的方法。在这篇综述中,我们总结了化疗过程中线粒体动力学的改变以及化疗药物与线粒体塑形蛋白协同作用的抗肿瘤机制。这些可能有助于揭示新的生物标志物,以更好地预测癌症化疗敏感性,并有助于开发有效的治疗策略用于癌症的临床治疗。