How ncRNAs control (immuno)metabolism in lung cancer: new biomarkers of chemo-immune-resistance, new druggable targets
Progetto Resistance to chemotherapy and to immune-killing limits the success of chemo-immuno-therapy in non-small cell lung cancers (NSCLC). One crucial player determining this double resistance is the endoplasmic reticulum stress-sensitive factor C/EBP-β, characterized by two splicing isoforms: LAP and LIP that are increased and decreased in cells with high mitochondrial oxidative metabolism, respectively. LAP up-regulates the drug efflux transporters ABCB1 and ABCC1, and down-regulates ABCA1, which favors immune-killing. LIP has opposite effects. Factors affecting LAP/LIP splicing are poorly known. Neither ABC transporters nor C/EBP-β are
druggable targets: alternative actionable circuitries to reverse chemo-immune-resistance must be found.