Bokil Ansooya, Sancho Patricia
IIS Aragon, Hospital Universitario Miguel Servet, Zaragoza 50009, Spain.
Cancer Drug Resist. 2019 Sep 19;2(3):634-646. doi: 10.20517/cdr.2019.46. eCollection 2019.
Chemoresistance constitute nowadays the major contributor to therapy failure in most cancers. There are main factors that mitigate cell response to therapy, such as target organ, inherent sensitivity to the administered compound, its metabolism, drug efflux and influx or alterations on specific cellular targets, among others. We now know that intrinsic properties of cancer cells, including metabolic features, substantially contribute to chemoresistance. In fact, during the last years, numerous reports indicate that cancer cells resistant to chemotherapy demonstrate significant alterations in mitochondrial metabolism, membrane polarization and mass. Metabolic activity and expression of several mitochondrial proteins are modulated under treatment to cope with stress, making these organelles central players in the development of resistance to therapies. Here, we review the role of mitochondria in chemoresistant cells in terms of metabolic rewiring and function of key mitochondria-related proteins.
如今，化疗耐药是大多数癌症治疗失败的主要原因。有多种主要因素会减轻细胞对治疗的反应，比如靶器官、对所施用化合物的固有敏感性、其代谢、药物外排与内流，或特定细胞靶点的改变等。我们现在知道，癌细胞的内在特性，包括代谢特征，在很大程度上导致了化疗耐药。事实上，在过去几年里，大量报告表明，对化疗耐药的癌细胞在线粒体代谢、膜极化和质量方面表现出显著改变。在治疗过程中，几种线粒体蛋白的代谢活性和表达会受到调节以应对压力，这使得这些细胞器成为耐药性发展的关键因素。在此，我们从代谢重编程和关键线粒体相关蛋白的功能方面综述线粒体在化疗耐药细胞中的作用。
