新加坡国立大学Vinay Tergaonkar等研究人员合作发现，通过RNA-RNA结合蛋白复合物对肿瘤微环境进行编程，可在IDH野生型胶质母细胞瘤中创造出一种可成药的脆弱性。2024年6月10日，国际知名学术期刊《自然—细胞生物学》杂志在线发表了这一成果。

为了增加治疗选择，研究人员调查了独特的RNA-RNA结合蛋白复合物LOC-DHX15。该复合物通过在癌症和免疫细胞之间建立反馈回路，在推动免疫细胞浸润和肿瘤生长方面发挥着至关重要的作用，从而增强了癌症的侵袭性。

利用可透过血脑屏障的小分子靶向这一复合物可提高疗效，破坏细胞通讯，并阻碍癌细胞存活和类干细胞特性。关注RNA-RNA结合蛋白的相互作用不仅是治疗没有IDH突变的胶质母细胞瘤的有希望的方法，也是癌症以外的潜在应用，为开发解决体内错综复杂的细胞关系的疗法提供了新的途径。

附：英文原文

Title: Tumour microenvironment programming by an RNA–RNA-binding protein complex creates a druggable vulnerability in IDH-wild-type glioblastoma

Author: Wu, Lele, Zhao, Zheng, Shin, Yong Jae, Yin, Yiyun, Raju, Anandhkumar, Vaiyapuri, Thamil Selvan, Idzham, Khaireen, Son, Miseol, Lee, Yeri, Sa, Jason K., Chua, Joelle Yi Heng, Unal, Bilal, Zhai, You, Fan, Wenhua, Huang, Lijie, Hu, Huimin, Gunaratne, Jayantha, Nam, Do-Hyun, Jiang, Tao, Tergaonkar, Vinay

Issue&Volume: 2024-06-10

Abstract: Patients with IDH-wild-type glioblastomas have a poor five-year survival rate along with limited treatment efficacy due to immune cell (glioma-associated microglia and macrophages) infiltration promoting tumour growth and resistance. To enhance therapeutic options, our study investigated the unique RNA–RNA-binding protein complex LOC–DHX15. This complex plays a crucial role in driving immune cell infiltration and tumour growth by establishing a feedback loop between cancer and immune cells, intensifying cancer aggressiveness. Targeting this complex with blood–brain barrier-permeable small molecules improved treatment efficacy, disrupting cell communication and impeding cancer cell survival and stem-like properties. Focusing on RNA–RNA-binding protein interactions emerges as a promising approach not only for glioblastomas without the IDH mutation but also for potential applications beyond cancer, offering new avenues for developing therapies that address intricate cellular relationships in the body.

DOI: 10.1038/s41556-024-01428-5

Source: https://www.nature.com/articles/s41556-024-01428-5