Key principles and guidance for the development of lncRNA targeting cancer therapeutics

Long non-coding RNAs (lncRNAs) have emerged as critical regulators of gene expression and cellular behavior in cancer, influencing tumor initiation, progression, metastasis, and therapeutic resistance. Their regulatory complexity and disease-specific expression patterns position them as promising yet challenging therapeutic targets.

This review summarizes current knowledge on the biological roles of lncRNAs in cancer and examines emerging therapeutic strategies designed to modulate their activity. The discussion integrates findings from recent genomic studies, functional screening approaches, and preclinical investigations of lncRNA-targeting modalities, including antisense oligonucleotides and other RNA-directed platforms. Key challenges related to target identification, delivery, specificity, and translational development are also addressed.

Although lncRNA-targeting therapeutics remain at an early stage of clinical translation, advances in RNA biology and drug delivery technologies are rapidly expanding their therapeutic potential. A rational framework integrating biological insight with translational considerations will be essential for guiding the development and clinical advancement of lncRNA-based cancer therapies.