Long non-coding RNAs (lncRNAs) provide a flexible and dynamic mechanism of gene expression regulation. Emerging evidence suggests a role for lncRNAs as key components in adaptation pathways. In breast cancer, transcriptional adaptation has been described to occur in particular during the acquisition of resistance to chemotherapeutics. We are currently characterizing the role of a group of lncRNAs during adaptive responses in triple-negative breast cancer cells by means of CRISPRinterference. We are functionalizing lncRNAs in a classic-drop out screening and in parallel, we are characterizing the transcriptomic response of lncRNAs modulation. With this work, we will bring novel knowledge into the regulatory framework played by lncRNAs in cancer cell plasticity.