摘要 IA015:识别和瞄准非整倍体(癌)细胞的合成致死性

IF 8.3 2区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY ACS Applied Materials & Interfaces Pub Date : 2024-06-10 DOI:10.1158/1538-8514.synthleth24-ia015
Uri Ben-David
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引用次数: 0

摘要

非整倍体是指染色体或染色体臂的数量不平衡,是癌细胞的遗传特征之一,但非整倍体仍是一个生物学谜团,也是癌症治疗中错失的良机。非整倍体细胞必须应对多种类型的细胞压力,这可能会产生合成致命性,可用于靶向非整倍体癌细胞。在这里,我将介绍我们在鉴定非整倍体状态的合成致死性(与特定复发性非整倍体的合成致死性相反)方面所做的努力。具体来说,我将重点介绍最近三项未发表的研究,我们在这些研究中报告了以下情况:(1)非整倍体细胞对纺锤体组装检查点(SAC)及其调控因子KIF18A的扰动具有优先敏感性;CDC20的表达和活性决定了对SAC抑制的敏感性。(2)非整倍体细胞依赖 MAPK 信号克服非整倍体诱导的 DNA 损伤;靶向 MAPK 信号可使非整倍体细胞对 DNA 损伤诱导剂和 PARP 抑制剂敏感。(3) 非整倍体细胞依赖 RNA 和蛋白质降解机制来减轻额外染色体对细胞造成的后果;这使得非整倍体细胞对抑制无义中间衰变、miRNA 介导的基因沉默和蛋白酶体复合物更为敏感。引用格式:乌里-本-大卫识别和靶向非整倍体(癌)细胞的合成致死性[摘要]。In:AACR 癌症研究特别会议论文集:扩展和转化癌症合成脆弱性;2024 年 6 月 10-13 日;加拿大魁北克省蒙特利尔。费城(宾夕法尼亚州):AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr IA015.
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Abstract IA015: Identifying and targeting synthetic lethalities of aneuploid (cancer) cells
Aneuploidy, an imbalanced number of chromosomes or chromosome arms, is a genetic hallmark of cancer cells, yet aneuploidy remains a biological enigma and a missed opportunity for cancer therapy. Aneuploid cells must cope with several types of cellular stresses, potentially creating synthetic lethalities that can be used to target aneuploid cancer cells. Here, I will describe our efforts to identify synthetic lethalities of the aneuploid state (in contrast to synthetic lethalities of specific recurrent aneuploidies. Specifically, I will focus on three recent unpublished studies, where we report that: (1) Aneuploid cells are preferentially sensitive to perturbation of the spindle assembly checkpoint (SAC) and its regulator KIF18A; the expression and activity of CDC20 determine the sensitivity to SAC inhibition. (2) Aneuploid cells depend on MAPK signaling for overcoming aneuploidy-induced DNA damage; targeting MAPK signaling can sensitize aneuploid cells to DNA damage inducing agents and to PARP inhibitors. (3) Aneuploid cells depend on RNA and protein degradation mechanisms to attenuate the cellular consequence of extra chromosomes; this renders aneuploid cells more sensitive to inhibition of nonsense-mediate decay, miRNA-mediated gene silencing, and the proteasome complex. Citation Format: Uri Ben-David. Identifying and targeting synthetic lethalities of aneuploid (cancer) cells [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr IA015.
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来源期刊
ACS Applied Materials & Interfaces
ACS Applied Materials & Interfaces 工程技术-材料科学:综合
CiteScore
16.00
自引率
6.30%
发文量
4978
审稿时长
1.8 months
期刊介绍: ACS Applied Materials & Interfaces is a leading interdisciplinary journal that brings together chemists, engineers, physicists, and biologists to explore the development and utilization of newly-discovered materials and interfacial processes for specific applications. Our journal has experienced remarkable growth since its establishment in 2009, both in terms of the number of articles published and the impact of the research showcased. We are proud to foster a truly global community, with the majority of published articles originating from outside the United States, reflecting the rapid growth of applied research worldwide.
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