Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar.
Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
Curr Opin Pharmacol. 2020 Oct;54:130-141. doi: 10.1016/j.coph.2020.09.012. Epub 2020 Nov 6.
Resistance in cancer cells to therapeutic measures is challenging and requires a rigorous delineation of the underlying mechanisms. Emerging findings reflect the characteristics of tumor cells to do the reprogramming of signaling machinery in order to overturn the therapeutic responses. Recent evidence shows that the tumor acquires drug resistance due to the presence of cancer stem cells (CSCs). Hence the understanding that how tumor cells reprogram their signaling mechanisms converging towards the stemness of CSCs is imperative for novel and effective therapy. This review outlines the current updates on how CSC-associated signaling pathways and its enhanced stemness trigger the development of drug resistance. Furthermore, we also discussed the strategies with a combinational approach that can simultaneously target both CSC-induced stemness and the resistance-related signaling pathways, which may provide an optimal outcome to overcome the problem of drug resistance in cancer therapy.
癌细胞对治疗措施的耐药性是一个挑战,需要严格阐明其潜在机制。新出现的研究结果反映了肿瘤细胞的特征,即重新编程信号机制,以推翻治疗反应。最近的证据表明,肿瘤由于存在癌症干细胞 (CSC) 而产生耐药性。因此,了解肿瘤细胞如何重新编程其信号机制,向 CSC 的干性趋同,对于新的有效治疗方法至关重要。本文综述了目前关于 CSC 相关信号通路及其增强的干性如何引发耐药性发展的最新进展。此外,我们还讨论了联合应用策略,该策略可以同时针对 CSC 诱导的干性和与耐药性相关的信号通路,这可能为克服癌症治疗中耐药性问题提供最佳结果。