Liver X receptors α (LXRα) and β (LXRβ) are members of the nuclear receptor family of transcription factors that control cholesterol homeostasis. LXRs regulate the gene expression of cholesterol transporters and fatty acid metabolism. In various cancer types, disturbances in cholesterol metabolism and transport have been linked to tumor growth, an immunosuppressive tumor microenvironment, and therapy resistance. Low expression of LXR target genes has been associated with poor clinical outcome and resistance to immunotherapy. Treatment with LXR agonists disrupts the cholesterol dependency of specific tumor types while boosting the immune response – this has been demonstrated in various pre-clinical models as well as in some heavily pretreated cancer patients. Thus, LXRs are an attractive target when it comes to treating patients with solid tumors, especially for tumors that fail to respond well to conventional therapies such as chemo and immunotherapy.
Lead Pharma has developed a proprietary series of potent and selective oral LXR agonists. Our LXR agonists have high target efficacy and show strong dose-dependent activityin a pre-clinical model of highly aggressive pre-clinical melanoma.