Department of Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, 3400 North Broad Street, Philadelphia, PA, 19140, USA.
Department of Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, 3400 North Broad Street, Philadelphia, PA, 19140, USA; Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, 604 Allison Road, Piscataway, NJ, 08854, USA.
Cancer Lett. 2018 Oct 1;433:53-64. doi: 10.1016/j.canlet.2018.06.034. Epub 2018 Jun 28.
The tumor microenvironment is complex with the cancer stem cell (CSC) as a member within its community. This population possesses the capacity to self-renew and to cause cellular heterogeneity of the tumor. CSCs are resistant to conventional anti-proliferative drugs. In order to be curative, it is imperative that CSCs must be eliminated by cancer therapy. A variety of dietary phytochemicals and repositioned drugs can act synergistically with conventional anti-cancer agents. In this review, we advocate the development of a novel approach, namely combination therapy by incorporating both phytochemicals and repositioned drugs to target CSCs. We cover select dietary phytochemicals (curcumin, resveratrol, EGCG, genistein) and repurposed drugs (metformin, niclosamide, thioridazine, chloroquine). Five of the eight (curcumin, resveratrol, EGCG, genistein, metformin) are listed in "The Halifax Project", that explores "the concept of a low-toxicity 'broad-spectrum' therapeutic approach that could simultaneously target many key pathways and mechanisms" [1]. For these compounds, we discuss their mechanisms of action, in which models their anti-CSC activities were identified, as well as advantages, challenges and potentials of combination therapy.
肿瘤微环境复杂,癌症干细胞(CSC)是其群落中的一员。该群体具有自我更新的能力,并导致肿瘤的细胞异质性。CSC 对常规抗增殖药物具有抗性。为了达到治愈效果,必须通过癌症治疗消除 CSC。各种膳食植物化学物质和再定位药物可以与常规抗癌药物协同作用。在这篇综述中,我们提倡开发一种新方法,即结合植物化学物质和再定位药物来靶向 CSC 的联合治疗。我们介绍了一些选择的膳食植物化学物质(姜黄素、白藜芦醇、表没食子儿茶素没食子酸酯、染料木黄酮)和再定位药物(二甲双胍、尼拉帕尼、硫利达嗪、氯喹)。其中有五种(姜黄素、白藜芦醇、表没食子儿茶素没食子酸酯、染料木黄酮、二甲双胍)被列入“哈利法克斯计划”,该计划探讨了“一种低毒性‘广谱’治疗方法的概念,该方法可以同时针对许多关键途径和机制”[1]。对于这些化合物,我们讨论了它们的作用机制,在哪些模型中确定了它们的抗 CSC 活性,以及联合治疗的优势、挑战和潜力。