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

Page view(s)
62
Checked on Feb 16, 2025
Tumour microenvironment programming by an RNA–RNA-binding protein complex creates a druggable vulnerability in IDH-wild-type glioblastoma
Title:
Tumour microenvironment programming by an RNA–RNA-binding protein complex creates a druggable vulnerability in IDH-wild-type glioblastoma
Journal Title:
Nature Cell Biology
Keywords:
Publication Date:
10 June 2024
Citation:
Wu, L., Zhao, Z., Shin, Y. J., Yin, Y., Raju, A., Vaiyapuri, T. S., Idzham, K., Son, M., Lee, Y., Sa, J. K., Chua, J. Y. H., Unal, B., Zhai, Y., Fan, W., Huang, L., Hu, H., Gunaratne, J., Nam, D.-H., Jiang, T., & Tergaonkar, V. (2024). Tumour microenvironment programming by an RNA–RNA-binding protein complex creates a druggable vulnerability in IDH-wild-type glioblastoma. Nature Cell Biology, 26(6), 1003–1018. https://doi.org/10.1038/s41556-024-01428-5
Abstract:
AbstractPatients 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.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
This research / project is supported by the National Research Foundation - Competitive Research Programme
Grant Reference no. : NRF-CRP26-2021-0001

This research / project is supported by the National Medical Research Council - Open Fund - Individual Research Grant
Grant Reference no. : OFIRG21jun-0101

This research / project is supported by the National Medical Research Council - Open Fund - Young Individual Research Grant
Grant Reference no. : OFYIRG21nov-0038

This research / project is supported by the A*STAR - Singapore Therapeutics Development Review
Grant Reference no. : H23H9a0013

This research / project is supported by the A*STAR - Career Development Fund
Grant Reference no. : 222D800036
Description:
ISSN:
1476-4679
1465-7392
Files uploaded:

File Size Format Action
ncb-paper.pdf 15.67 MB PDF Open