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.

IDH野生型胶质母细胞瘤患者的五年生存率较差，而且由于免疫细胞（胶质瘤相关小胶质细胞和巨噬细胞）浸润促进肿瘤生长和抵抗，治疗效果有限。为了增强治疗选择，我们的研究调查了独特的 RNA-RNA 结合蛋白复合物 LOC-DHX15。这种复合物通过在癌症和免疫细胞之间建立反馈回路，增强癌症的侵袭性，在驱动免疫细胞浸润和肿瘤生长方面发挥着至关重要的作用。用血脑屏障渗透性小分子靶向这种复合物可以提高治疗效果，破坏细胞通讯并阻碍癌细胞存活和干细胞样特性。关注 RNA-RNA 结合蛋白相互作用不仅对于没有 IDH 突变的胶质母细胞瘤来说是一种有前景的方法，而且对于癌症以外的潜在应用也很有前景，为开发解决体内复杂细胞关系的疗法提供了新途径。