The Walter and Eliza Hall Institute, Parkville, VIC, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia; Genome Engineering and Cancer Modelling Program, Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia; School of Cancer Medicine, La Trobe University, Bundoora, VIC, Australia.
The Walter and Eliza Hall Institute, Parkville, VIC, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
Dev Cell. 2024 Oct 7;59(19):2532-2548. doi: 10.1016/j.devcel.2024.06.018.
From its earliest characterization, it has been recognized that there is a role for regulated (programmed) cell death in cancer. As our understanding of the different types of programmed cell death processes and their molecular control has advanced, so have the technologies that allow us to manipulate these processes to, for example, fight against cancer. In this review, we describe the roles of the different forms of regulated cell death in the development of cancer as well as their potential therapeutic exploitation. In that vein, we explore the development and use of BH3-mimetics, a unique class of drugs that can directly activate the apoptotic cell death machinery to treat cancer. Finally, we address key challenges that face the field to improve the use of these therapeutics and the efforts that are being undertaken to do so.
从最早的特征描述开始，人们就已经认识到，在癌症中，有一个受调控（程序性）细胞死亡的角色。随着我们对不同类型的程序性细胞死亡过程及其分子控制的理解的提高，我们也开发出了能够操纵这些过程的技术，例如，对抗癌症。在这篇综述中，我们描述了不同形式的受调控细胞死亡在癌症发展中的作用，以及它们潜在的治疗利用。在这方面，我们探讨了 BH3 模拟物的开发和应用，BH3 模拟物是一类独特的药物，它可以直接激活细胞凋亡的死亡机制来治疗癌症。最后，我们解决了该领域面临的关键挑战，以提高这些治疗方法的应用，并努力做到这一点。
