Division of Applied Medicine and Therapeutics, School of Medicine and Dentistry, University of Aberdeen, Aberdeen AB25 2ZD, UK.
Curr Pharm Des. 2014;20(2):201-22. doi: 10.2174/13816128113199990031.
Tumour cell death is required for the clearance of malignant cells and is a vital part of the mechanism of natural tumour suppression. Cancer cells, having acquired multiple deregulated pathways involving several cellular oragenelles, are capable of disrupting these normally finely tuned processes thereby evading both physiological and therapeutic intervention. Although current available data indicate the dependence of successful tumour cell clearance on classical apoptotic pathways (intrinsic and/or extrinsic pathways), there is now evidence suggesting that alternative apoptotic and non-apoptotic pathways may effectively contribute to tumour cell death. The mitochondria, proteasomes, endoplasmic reticulum, Golgi apparatus, lysosomes and lysosome-related organelles of tumour cells exhibit a number of deregulations which have been identified as potential druggable targets for successful rational drug design and therapy. In this review, we summarise the roles of these cellular organelles in tumour initiation and establishment as well as current trends in development of agents that target deregulations in these organelles.
肿瘤细胞死亡是清除恶性细胞所必需的，也是天然肿瘤抑制机制的重要组成部分。癌细胞获得了涉及多个细胞细胞器的多种失调途径，能够破坏这些正常的精细调节过程，从而逃避生理和治疗干预。尽管目前可用的数据表明成功清除肿瘤细胞依赖于经典的凋亡途径（内在和/或外在途径），但现在有证据表明，替代的凋亡和非凋亡途径可能有效地有助于肿瘤细胞死亡。肿瘤细胞的线粒体、蛋白酶体、内质网、高尔基体、溶酶体和溶酶体相关细胞器表现出许多失调，这些失调已被确定为成功进行合理药物设计和治疗的潜在可用药靶标。在这篇综述中，我们总结了这些细胞器在肿瘤发生和建立中的作用，以及针对这些细胞器失调的药物开发的当前趋势。
