Functional, Pharmacogenomic, and Immune Landscapes of Long Non‐Coding RNAs in Cancer

Abstract Long non‐coding RNAs (lncRNAs) are emerging as key regulators in cancer, with significant potential as diagnostic, prognostic, and therapeutic targets. Here, this work systematically analyzes lncRNA associations with targeted therapies and immunotherapies across 33 cancer types using The Cancer Genome Atlas (TCGA) and real‐world datasets. This work identifies 53,173 lncRNA‐pathway associations, millions of lncRNA‐drug response associations (via CancerRxTissue and VAEN), and extensive correlations with immune checkpoints and infiltration. This work further identifies 69 lncRNAs associated with immunotherapy response and 2,611 differentially expressed lncRNAs between low and high objective response rate (ORR) groups. Additionally, two lncRNAs are correlated with immune‐related adverse events (irAEs), and 1,376 lncRNAs exhibited expression differences between cancers with low and high irAE risk. To facilitate further research, this work develops PILNC ( https://hanlaboratory.com/PILNC ), a comprehensive web portal enabling exploration of lncRNA associations with cancer pathways, drug responses, immune features, and immunotherapy outcomes.