癌症中凋亡脆弱性的内源性和外源性决定因素。
Endogenous and imposed determinants of apoptotic vulnerabilities in cancer.
机构信息
Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA.
出版信息
Trends Cancer. 2023 Feb;9(2):96-110. doi: 10.1016/j.trecan.2022.10.004. Epub 2022 Oct 28.
Abstract
The intrinsic apoptosis pathway is controlled by the BCL-2 family of proteins. Although the pro-survival members of this family can help cancer cells evade apoptosis, they may also produce apoptotic vulnerabilities that can potentially be exploited therapeutically. Apoptotic vulnerabilities can be driven by endogenous factors including altered genetics, signaling, metabolism, structure and lineage or differentiation state as well as imposed factors, the most prominent being exposure to anti-cancer agents. The recent development of BH3 mimetics that inhibit pro-survival BCL-2 family proteins has allowed these apoptotic vulnerabilities to be targeted with demonstrable clinical success. Here, we review the key concepts that are vital for understanding, uncovering, and exploiting apoptotic vulnerabilities in cancer for the potential improvement of patient outcomes.
摘要
内在凋亡途径由 BCL-2 蛋白家族控制。尽管该家族的促生存成员可以帮助癌细胞逃避凋亡，但它们也可能产生潜在的治疗靶点凋亡脆弱性。凋亡脆弱性可由内在因素驱动，包括遗传改变、信号转导、代谢、结构和谱系或分化状态，以及外在因素，其中最突出的是暴露于抗癌药物。最近开发的 BH3 模拟物可以抑制促生存 BCL-2 家族蛋白，这使得靶向这些凋亡脆弱性具有明显的临床成功。在这里，我们回顾了理解、揭示和利用癌症中凋亡脆弱性的关键概念，以期潜在地改善患者的预后。
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