Targeting ncRNAs to overcome metabolic reprogramming‑mediated drug resistance in cancer (Review)

The emergence of resistance to antitumor drugs in cancer cells presents a notable obstacle in cancer therapy. Metabolic reprogramming is characterized by enhanced glycolysis, disrupted lipid metabolism, glutamine dependence and mitochondrial dysfunction. In addition to promoting tumor growth and metastasis, metabolic reprogramming mediates drug resistance through diverse molecular mechanisms, offering novel opportunities for therapeutic intervention. Non‑coding RNAs (ncRNAs), a diverse class of RNA molecules that lack protein‑coding function, represent a notable fraction of the human genome. Due to their distinct expression profiles and multifaceted roles in various cancers, ncRNAs have relevance in cancer pathophysiology. ncRNAs orchestrate metabolic abnormalities associated with drug resistance in cancer cells. The present review provides a comprehensive analysis of the mechanisms by which metabolic reprogramming drives drug resistance, with an emphasis on the regulatory roles of ncRNAs in glycolysis, lipid metabolism, mitochondrial dysfunction and glutamine metabolism. Furthermore, the present review aimed to discuss the potential of ncRNAs as biomarkers for predicting chemotherapy responses, as well as emerging strategies to target ncRNAs that modulate metabolism, particularly in the context of combination therapy with anti‑cancer drugs.