lncRNAs as Targetable Nodes of Oncogenic Networks Underlying Cancer Progression and Therapy Resistance

The human cancer genome contains a substantial proportion of nonconserved regions that are transcribed into long noncoding RNAs (lncRNAs) and hosted in areas recurrently implicated in cancer. Due to its high responsiveness to extracellular cues, the aberrant lncRNA transcriptome represents a major source of molecular innovation for cancer cells, which are subjected to intense evolutionary pressure during progression and therapy resistance. As such, lncRNAs contribute to the aberrant rewiring of the molecular networks in cancer cells by functioning as molecular sponges and scaffolds, modulating the activity and localization of other biomolecules. This largely untapped reservoir of regulatory elements holds significant potential for addressing the current clinical challenges of cancer progression and therapy resistance. This review synthesizes current insights into the molecular strategies by which lncRNAs subvert homeostatic regulation across diverse cellular compartments and within the extracellular milieu. Further, it explores their multifaceted contributions to cancer therapy resistance, underscoring their emerging prominence as both actionable therapeutic targets and informative biomarkers.