School of Life Health and Chemical Sciences, The Open University, Milton Keynes, UK.
Prostate Cancer Targeted Therapy Group, The Institute of Cancer Research, Sutton, UK; Department of Clinical Medicine, University of Naples 'Federico II', Naples, Italy.
Trends Pharmacol Sci. 2018 Aug;39(8):695-709. doi: 10.1016/j.tips.2018.05.002. Epub 2018 Jun 8.
Taxanes are chemotherapeutic drugs employed in the clinic to treat a variety of malignancies. Despite their overall efficacy, cancer cells often display resistance to taxanes. Therefore, new strategies to increase the effectiveness of taxane-based chemotherapeutics are urgently needed. Multiple molecular players are linked to taxane resistance; these include efflux pumps, DNA repair mechanisms, and hypoxia-related pathways. In addition, emerging evidence indicates that both non-coding RNAs and epigenetic effectors might also be implicated in taxane resistance. Here we focus on the causes of taxane resistance, with the aim to envisage an integrated model of the 'taxane resistance phenome'. This model could help the development of novel therapeutic strategies to treat taxane-resistant neoplasms.
紫杉烷类是临床上用于治疗多种恶性肿瘤的化疗药物。尽管紫杉烷类药物总体上有效,但癌细胞常常对紫杉烷类药物产生耐药性。因此,迫切需要新的策略来提高基于紫杉烷类的化疗药物的疗效。多种分子参与者与紫杉烷类耐药性有关;这些包括外排泵、DNA 修复机制和缺氧相关途径。此外,新出现的证据表明,非编码 RNA 和表观遗传效应物也可能与紫杉烷类耐药性有关。在这里,我们重点关注紫杉烷类耐药性的原因,旨在设想一个“紫杉烷类耐药表型”的综合模型。该模型有助于开发治疗紫杉烷类耐药性肿瘤的新治疗策略。