Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.
Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.
Pharm Res. 2023 Nov;40(11):2699-2714. doi: 10.1007/s11095-023-03595-w. Epub 2023 Sep 19.
Since ancient times, dietary phytochemicals are known for their medicinal properties. They are broadly classified into polyphenols, terpenoids, alkaloids, phytosterols, and organosulfur compounds. Currently, there is considerable interest in their potential health effects against various diseases, including lung cancer. Lung cancer is the leading cause of cancer deaths with an average of five-year survival rate of lung cancer patients limited to just 14%. Identifying potential early molecular biomarkers of pre-malignant lung cancer cells may provide a strong basis to develop early cancer detection and interception methods. In this review, we will discuss molecular changes, including genetic alterations, inflammation, signal transduction pathways, redox imbalance, epigenetic and proteomic signatures associated with initiation and progression of lung carcinoma. We will also highlight molecular targets of phytochemicals during lung cancer development. These targets mainly consist of cellular signaling pathways, epigenetic regulators and metabolic reprogramming. With growing interest in natural products research, translation of these compounds into new cancer prevention approaches to medical care will be urgently needed. In this context, we will also discuss the overall pharmacokinetic challenges of phytochemicals in translating to humans. Lastly, we will discuss clinical trials of phytochemicals in lung cancer patients.
自古以来,膳食植物化学物质就因其药用特性而闻名。它们被广泛分为多酚类、萜类、生物碱、植物固醇和有机硫化合物。目前,人们对它们在预防各种疾病(包括肺癌)方面的潜在健康影响非常感兴趣。肺癌是癌症死亡的主要原因,肺癌患者的平均五年生存率仅为 14%。确定潜在的癌前肺癌细胞的早期分子生物标志物,可能为开发早期癌症检测和干预方法提供坚实的基础。在这篇综述中,我们将讨论与肺癌发生和发展相关的分子变化,包括遗传改变、炎症、信号转导途径、氧化还原失衡、表观遗传和蛋白质组学特征。我们还将重点介绍植物化学物质在肺癌发展过程中的分子靶点。这些靶点主要包括细胞信号通路、表观遗传调控因子和代谢重编程。随着对天然产物研究的兴趣日益浓厚,将这些化合物转化为新的癌症预防方法应用于医疗保健将是迫切需要的。在这方面,我们还将讨论植物化学物质在转化为人体时的整体药代动力学挑战。最后,我们将讨论肺癌患者中植物化学物质的临床试验。