Maloney Sara M, Hoover Camden A, Morejon-Lasso Lorena V, Prosperi Jenifer R
Harper Cancer Research Institute, South Bend, IN 46617, USA.
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, South Bend, IN 46617, USA.
Cancers (Basel). 2020 Nov 10;12(11):3323. doi: 10.3390/cancers12113323.
The taxane family of chemotherapy drugs has been used to treat a variety of mostly epithelial-derived tumors and remain the first-line treatment for some cancers. Despite the improved survival time and reduction of tumor size observed in some patients, many have no response to the drugs or develop resistance over time. Taxane resistance is multi-faceted and involves multiple pathways in proliferation, apoptosis, metabolism, and the transport of foreign substances. In this review, we dive deeper into hypothesized resistance mechanisms from research during the last decade, with a focus on the cancer types that use taxanes as first-line treatment but frequently develop resistance to them. Furthermore, we will discuss current clinical inhibitors and those yet to be approved that target key pathways or proteins and aim to reverse resistance in combination with taxanes or individually. Lastly, we will highlight taxane response biomarkers, specific genes with monitored expression and correlated with response to taxanes, mentioning those currently being used and those that should be adopted. The future directions of taxanes involve more personalized approaches to treatment by tailoring drug-inhibitor combinations or alternatives depending on levels of resistance biomarkers. We hope that this review will identify gaps in knowledge surrounding taxane resistance that future research or clinical trials can overcome.
紫杉烷类化疗药物已被用于治疗多种主要源自上皮组织的肿瘤,并且仍是某些癌症的一线治疗药物。尽管在一些患者中观察到生存时间延长和肿瘤大小缩小,但许多患者对这些药物没有反应或随着时间推移产生耐药性。紫杉烷耐药性是多方面的,涉及增殖、凋亡、代谢和外来物质转运等多个途径。在本综述中,我们将更深入地探讨过去十年研究中假设的耐药机制,重点关注将紫杉烷作为一线治疗药物但经常对其产生耐药性的癌症类型。此外,我们将讨论目前的临床抑制剂以及尚未获批的、靶向关键途径或蛋白质并旨在与紫杉烷联合使用或单独使用以逆转耐药性的抑制剂。最后,我们将强调紫杉烷反应生物标志物,即那些监测其表达并与对紫杉烷的反应相关的特定基因,提及目前正在使用的以及应该采用的生物标志物。紫杉烷的未来发展方向涉及根据耐药生物标志物水平定制药物 - 抑制剂组合或替代方案,从而采用更个性化的治疗方法。我们希望本综述能够找出围绕紫杉烷耐药性的知识空白,以便未来的研究或临床试验能够加以克服。