Centre for Biosystems and Genome Network Medicine, Ioannina University, Ioannina, Greece; Department of Surgery, Ioannina University Hospital, Ioannina, Greece.
Centre for Biosystems and Genome Network Medicine, Ioannina University, Ioannina, Greece; Department of Surgery, 'G. Hatzikosta' General Hospital, Ioannina, Greece.
Drug Discov Today. 2019 Jun;24(6):1281-1294. doi: 10.1016/j.drudis.2019.04.008. Epub 2019 Apr 19.
Progress in understanding and overcoming fatal intrinsic and acquired resistance is slow, with only a few exceptions. Despite advances in modern genome and transcriptome analysis, the controversy of the three different theories on drug resistance and tumor progression, namely dynamic intratumor heterogeneity, pre-existing minor genomic clones and tumor ecosystem, is unresolved. Moreover, evidence on transcriptional heterogeneity suggests the necessity of a drug bank for individualized, precise drug-sensitivity prediction. We propose a cancer type- and stage-specific clinicogenomic and tumor ecosystemic concept toward cancer precision medicine, focusing on early therapeutic resistance and relapse.
在理解和克服致命的内在和获得性耐药方面进展缓慢，仅有少数例外。尽管现代基因组和转录组分析取得了进展，但关于耐药性和肿瘤进展的三种不同理论，即肿瘤内异质性的动态变化、预先存在的少量基因组克隆和肿瘤生态系统，仍存在争议。此外，转录异质性的证据表明有必要建立一个药物库，以进行个体化的、精确的药物敏感性预测。我们提出了一个针对癌症精准医学的基于癌症类型和分期的临床基因组学和肿瘤生态系统概念，重点关注早期治疗耐药和复发。
