Long non-coding RNAs as modulators of endocrine therapy response in hormone receptor-positive breast cancer.

Breast cancer is a major cause of cancer-related mortality among women, with hormone receptor-positive (HR+) breast cancer accounting for 70-80% of diagnosed cases. The current treatment approaches include both endocrine monotherapy and combinational strategies incorporating targeted signaling pathway inhibitors. Despite recent therapeutic advances that have significantly improved patient outcomes, the development of resistance to endocrine therapies leads to relapses and treatment failure. Emerging evidence has shown that long non-coding RNAs (lncRNAs) are therapeutic modulators; however, their involvement in clinical studies has not been much explored. In HR+ breast cancer, lncRNAs influence both sensitivity and resistance to endocrine therapy by modulating estrogen receptor (ER) function, switching between alternative survival pathways, and altering tumor epigenetics and tumor microenvironment. The major focus of this comprehensive review is to understand the role of lncRNAs in overcoming the endocrine resistance issues in the treatment of HR+ breast cancer. It presents a comprehensive approach focused on endocrine therapy mechanisms, resistance, and adaptive escape pathways of HR+ tumor cells. By mapping these mechanisms of endocrine therapy, the review reveals novel therapeutic targets for the treatment of HR+ breast cancer. Lastly, it highlights the specialized lncRNA-based therapeutics for bone metastatic niches in HR+ breast cancer and current approaches of therapeutic targeting of lncRNAs for disease treatment.