Moschovi Maria, Critselis Elena, Cen Osman, Adamaki Maria, Lambrou George I, Chrousos George P, Vlahopoulos Spiros
a 1 University of Athens, Horemio Research Institute, First Department of Pediatrics, Thivon & Levadeias, Goudi, Athens, 11527, Greece.
b 2 University of Athens, Pediatric Hematology/Oncology Unit, First Department of Pediatrics, University of Athens, "Aghia Sofia" Children's Hospital, Thivon & Levadeias, 11527 Goudi, Athens, Greece.
Expert Rev Anticancer Ther. 2015;15(12):1405-17. doi: 10.1586/14737140.2015.1095095. Epub 2015 Nov 2.
Cancer treatment aims to exploit properties that define malignant cells. In recent years, it has become apparent that malignant cells often survive cancer treatment and ensuing cell stress by switching on auxiliary turnover pathways, changing cellular metabolism and, concomitantly, the gene expression profile. The changed profile impacts the material exchange of cancer cells with affected tissues. Herein, we show that pathways of proteostasis and energy generation regulate common transcription factors. Namely, when one pathway of intracellular turnover is blocked, it triggers alternative turnover mechanisms, which induce transcription factor proteins that control expression of cytokines and regulators of apoptosis, cell division, differentiation, metabolism, and response to hormones. We focus on several alternative turnover mechanisms that can be blocked by drugs already used in clinical practice for the treatment of other non-cancer related diseases. We also discuss paradigms on the challenges posed by cancer cell adaptation mechanisms.
癌症治疗旨在利用恶性细胞的特性。近年来，很明显恶性细胞常常通过开启辅助周转途径、改变细胞代谢以及随之改变基因表达谱来在癌症治疗及后续的细胞应激中存活下来。改变后的谱会影响癌细胞与受影响组织之间的物质交换。在此，我们表明蛋白质稳态和能量生成途径调节共同的转录因子。也就是说，当细胞内周转的一条途径被阻断时，它会触发替代周转机制，这些机制会诱导控制细胞因子表达以及细胞凋亡、细胞分裂、分化、代谢和激素反应调节因子表达的转录因子蛋白。我们关注几种可以被临床实践中已用于治疗其他非癌症相关疾病的药物阻断的替代周转机制。我们还讨论了癌细胞适应机制所带来挑战的范例。
