Large-scale drug sensitivity, gene dependency, and proteogenomic analyses of telomere maintenance mechanisms in cancer cells
Yangxiu Wu, Zhaoxiang Cai, Daniel Cross, Jan R Noble, Karen Prest, James Littleboy, Scott B Cohen, Bjorn Edlundh, Jennifer M S Koh, Renhua Xu, Zaynab Noor, Marjan Bastami, Sara Valentini, Laura Richardson, Syd Barthorpe, Nima Arymanesh, Phillip J Robinson, Peter G Hains, Mathew J Garnett, Karen L MacKenzie
Abstract
Telomere maintenance is a hallmark of cancer. Here, we present a large-scale analysis of telomere maintenance mechanisms (TMMs) in 976 cancer cell lines. Integrating proteomic, genomic, and transcriptomic data with drug sensitivity and CRISPR-Cas9 gene essentiality screens, we identify molecular features associated with telomerase activity and Alternative Lengthening of Telomeres (ALT). We discover broad heterogeneity in telomere biology beyond the binary TMM classification and develop multi-omic predictors for TMM status. Our findings reveal potential therapeutic vulnerabilities linked to specific TMMs, providing a resource for developing telomere-targeted cancer therapies.
BibTeX
@article{wu2025wu2025telomere,
title = {{Large-scale drug sensitivity, gene dependency, and proteogenomic analyses of telomere maintenance mechanisms in cancer cells}},
author = {Yangxiu Wu and Zhaoxiang Cai and Daniel Cross and Jan R Noble and Karen Prest and James Littleboy and Scott B Cohen and Bjorn Edlundh and Jennifer M S Koh and Renhua Xu and Zaynab Noor and Marjan Bastami and Sara Valentini and Laura Richardson and Syd Barthorpe and Nima Arymanesh and Phillip J Robinson and Peter G Hains and Mathew J Garnett and Karen L MacKenzie},
journal = {Nature Communications},
year = {2025},
doi = {10.1038/s41467-025-67190-w}
}