LncRNAs driving feedback loops to boost drug resistance: sinuous pathways in cancer

Feedback loops mediate signaling pathways to maintain cellular homeostasis. There are two types, positive and negative feedback loops. Both are subject to alterations, and consequently can become pathogenic in the development of diseases such as cancer. Long noncoding RNAs (lncRNAs) are regulators of signaling pathways through feedback loops hidden as the dark regulatory elements yet to be described with great impact on cancer tumorigenesis, development, and drug resistance. Several feedback loops have been studied in cancer, however, how they are regulated by lncRNAs is hardly evident, setting a trending topic in oncological research. In this review, we recapitulate and discuss the feedback loops that are regulated by lncRNAs to promote drug resistance. Furthermore, we propose additional strategies that allow us to identify, analyze and comprehend feedback loops regulated by lncRNAs to induce drug resistance or even to gain insight into novel feedback loops that are stimulated under the pressure of treatment and consequently increase its efficacy. This knowledge will be useful to optimize the therapeutic use of oncological drugs. •Long noncoding RNAs (lncRNAs) as the main regulatory actors of feedback loops in cancer.•LncRNAs feedback loops are master regulators of signaling with impact in cancer tumorigenesis and drug resistance.•Feedback loops as key regulators, can play several roles in a pathogenic or therapeutic way in response to a stimulus.