biostudies-literatureWang RNICHD NIH HHSNHLBI NIH HHSDoD DMDRP Idea Development AwardNational Institutes of Healththe National Institutes of Health (NIH)HESI THRIVE awardNHGRI NIH HHSNCI NIH HHSNINDS NIH HHSWelch FoundationNIH HHSNIGMS NIH HHSNIH R01National Science Foundatione13414https://www.ebi.ac.uk/biostudies/studies/S-EPMC12866694biostudies-literatureUnknown13(6)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.Advanced science (Weinheim, Baden-Wurttemberg, Germany)Functional, Pharmacogenomic, and Immune Landscapes of Long Non-Coding RNAs in Cancer.PMC12866694#2 138 259U01HL156059R01NS12792261561R01 CA269489R01 CA285454R01GM136922R01 CA231011R01 HD110520#2 138 296R01HG011633U01 HL156059R01CA262623AU‐2000‐20220331#2 138 307R01 GM136922R01 NS127922#2 138 286#2 137 603R01HD110520R01 HG011633R01CA285454AU-2000-20220331R01CA269489MD200001R01 CA262623R01 CA255080Diao LYang JMa LYang LHan LZang YChen CLi WLiu YLim BLin CWang RDing SLuo MWengler JChen YfalseFunctional, Pharmacogenomic, and Immune Landscapes of Long Non-Coding RNAs in Cancer.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.2026-01-01T00:00:00Z2026 Jan2026-07-05T03:10:35.573Z2026-07-05T03:08:21.607ZS-EPMC128666944127008810.1002/advs.202513414