Therapeutic resistance in cancer: lncRNAs as modulators and targets for cancer therapy

Therapeutic resistance continues to be a significant challenge in cancer treatment, often leading to tumor recurrence, metastasis, and limited therapeutic efficacy despite advancements in chemotherapy and radiotherapy. This resistance arises from complex molecular mechanisms that are influenced by various factors, including genetic alterations, epigenetic modifications, and cellular signaling. Recently, lncRNAs, a subclass of non-coding RNAs, have gained prominence for their essential role in driving cancer progression and mediating resistance to therapy. The resistance phenotype is shaped by lncRNAs through the regulation of key signaling pathways, DNA repair mechanisms, and cellular survival processes. For example, lncRNAs such as HOTAIR and MALAT1 are involved in the regulation of PI3K/AKT, EMT, and DNA repair pathways, and influence cell proliferation, apoptosis, and metastasis. These findings underscore the potential of lncRNAs as therapeutic targets. Targeting lncRNA-mediated pathways offers a promising approach to overcome resistance and enhance the efficacy of existing therapies. This review provides an in-depth analysis of the molecular mechanisms by which lncRNAs mediate resistance in various cancers, such as gastric cancer, lung cancer, breast cancer, and hepatocellular carcinoma. By focusing on the therapeutic potential of lncRNAs, we propose new avenues for overcoming resistance and improving treatment outcomes in cancer therapy.