State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute For Applied Research in Medicine and Health, Macau University of Science and Technology, Macau (SAR), China.
School of Pharmacy & State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, China.
Antioxid Redox Signal. 2021 May 10;34(14):1108-1127. doi: 10.1089/ars.2020.8125. Epub 2020 Dec 3.
The 2019 Nobel Prize awarded to the mechanisms for oxygen sensing and adaptation according to oxygen availability, highlighting the fundamental importance of gaseous molecules. Gaseous molecules, including reactive oxygen species (ROS), can interact with different cations generated during metabolic and redox dysregulation in cancer cells. Cross talk between calcium signaling and metabolic/redox pathways leads to network-based dyregulation in cancer. Recent discovery on using small molecules targeting the ion channels, redox signaling, and protein modification on metabolic enzymes can effectively inhibit cancer growth. Several FDA-approved drugs and clinical trials are ongoing to target the calcium channels, such as TRPV6 and TRPM8. Multiple small molecules from natural products target metablic and redox enzymes to exert an anticancer effect. Small molecules targeting key ion channels, metabolic enzymes that control key aspects of metabolism, and redox proteins are promising, but their action mechanisms of the target are needed to be elucidated with advanced-omic technologies, which can give network-based and highly dimensioal data. In addition, small molecules that can directly modify the protein residues have emerged as a novel anticancer strategy. Advanced technology accelerates the detection of ions and metabolic and redox changes in clinical samples for diagnosis and informs the decision of cancer treatment. The improvement of ROS detection, ROS target identification, and computational-aid drug discovery also improves clincal outcome.Overall, network-based or holistic regulations of cancer ion therapy and metabolic and redox intervention are promising as new anticancer strategies. . 34, 1108-1127.
2019 年诺贝尔生理学或医学奖授予氧感应和适应机制，根据氧气可用性，突出了气体分子的基本重要性。气体分子，包括活性氧物种（ROS），可以与癌细胞代谢和氧化还原失调期间产生的不同阳离子相互作用。钙信号和代谢/氧化还原途径之间的串扰导致癌症中的基于网络的失调。最近发现使用靶向离子通道、氧化还原信号和代谢酶蛋白修饰的小分子可以有效抑制癌症生长。几种已批准用于靶向钙通道的 FDA 药物和临床试验正在进行中，例如 TRPV6 和 TRPM8。来自天然产物的多种小分子靶向代谢和氧化还原酶以发挥抗癌作用。靶向控制代谢关键方面的关键离子通道和代谢酶以及氧化还原蛋白的小分子具有很大的潜力，但需要使用先进的组学技术阐明其作用机制，这些技术可以提供基于网络和高度多维的数据。此外，能够直接修饰蛋白质残基的小分子已成为一种新的抗癌策略。先进的技术加速了对临床样本中离子和代谢及氧化还原变化的检测，用于诊断并为癌症治疗决策提供信息。ROS 检测、ROS 靶点鉴定和计算辅助药物发现的改进也改善了临床结果。总体而言，基于网络或整体的癌症离子治疗和代谢及氧化还原干预调节作为新的抗癌策略具有很大的前景。34,1108-1127。
