LncRNAs as regulators of chemoresistance and chemosensitivity in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype of breast cancer, characterized by significant heterogeneity and high recurrence rates. Due to this heterogeneity, TNBC often develops resistance to chemotherapy, leading to aggressive clinical behavior and poor prognosis. Long non-coding RNAs (lncRNAs), defined as RNAs longer than 500 nucleotides that act at both transcriptional and post-transcriptional levels, influence therapeutic responses in TNBC through various molecular mechanisms, thereby directly impacting treatment effectiveness and patient outcomes. Importantly, lncRNAs have a dual, context-dependent role in TNBC, either promoting chemoresistance or enhancing chemosensitivity by functioning as competing endogenous RNAs, regulating epigenetic processes, stabilizing mRNAs and proteins, and affecting DNA damage repair, apoptosis, autophagy, epithelial-mesenchymal transition, and pro-survival signaling pathways. These functions indicate their potential as therapeutic targets and biomarkers for personalized treatment. In this review, we examine the biological functions of lncRNAs in TNBC, highlighting their molecular mechanisms and clinical significance. We also review evidence on how lncRNAs contribute to therapeutic resistance and sensitivity and explore emerging perspectives on their potential as biomarkers and therapeutic targets for TNBC management.