Department of Surgery &Cancer, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, UK.
Nat Rev Cancer. 2014 Nov;14(11):747-53. doi: 10.1038/nrc3819. Epub 2014 Sep 25.
Epigenetic events, which are somatically inherited through cell division, are potential drivers of acquired drug resistance in cancer. The high rate of epigenetic change in tumours generates diversity in gene expression patterns that can rapidly evolve through drug selection during treatment, leading to the development of acquired resistance. This will potentially confound stratified chemotherapy decisions that are solely based on mutation biomarkers. Poised epigenetic states in tumour cells may drive multistep epigenetic fixation of gene expression during the acquisition of drug resistance, which has implications for clinical strategies to prevent the emergence of drug resistance.
表观遗传事件可通过细胞分裂在体细胞中遗传，是癌症获得性药物耐药的潜在驱动因素。肿瘤中表观遗传变化的高频率会导致基因表达模式的多样性，这种多样性可以在治疗过程中通过药物选择迅速进化，从而导致获得性耐药的发展。这可能会混淆仅基于突变生物标志物的分层化疗决策。肿瘤细胞中处于休眠状态的表观遗传状态可能会在获得耐药性的过程中驱动基因表达的多步表观遗传固定，这对预防耐药性出现的临床策略具有重要意义。
