Alterations in lipid- and cholesterol-associated pathways are widely described in tumor cells. Recent evidences suggest that the Stearoyl CoA desaturase-1 (SCD1), the enzyme that produces Monounsaturated Fatty Acids, plays a key role in several solid cancers. Based on previous results obtained in our laboratory that point to SCD1 as an important factor for lung cancer stem cells, we aim at deepening the role of SCD1 and cholesterol metabolism in lung cancer stem cells. This study will assess whether blockade of SCD1 or other enzymes in lipid metabolism increases immunogenicity of the cells by inducing changes in expression of proteins involved in immunological pathways. The project will provide mechanistic insights onto the role of SCD1 in lung cancer initiating cells immune avoidance and will demonstrate if lipid metabolism can be considered as a target to treat lung cancer in combination with immunotherapies.
Despite the advances in the early diagnosis and the generation of new targeted therapies, lung cancer is still the leading cause of cancer related mortality worldwide. Most of the treatment failure is caused by the onset of resistance to chemotherapies and the limited efficacy of the targeted therapies now available. Many evidences demonstrated the existence of cancer stem initiating cells inside tumors. This population of cells, which shows stem cell traits, results resistant to conventional chemotherapies and likely responsible of tumor relapse. Therefore, targeting cancer stem cells could contribute to improve the current treatment. With the present research we will demonstrate whether inhibiting SCD1 could result in cancer stem cells inhibition and will provide evidences whether SCD1 inhibitors could be an effective strategy to improve immunogenicity immunotherapy for NSCLC.