Investigating the role of the Liver X Receptor in Potentiating Mitotane Therapy in Adrenocortical Carcinoma

Abstract

Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy. Adjuvant mitotane improves survival but is limited by its narrow therapeutic window and escape from therapeutic efficacy. Mitotane modulates its adrenolytic effect through SOAT1 antagonism and consequent free cholesterol accumulation. Liver X receptors (LXRs), are highly expressed in adrenal tissue and mediate cholesterol homeostasis. We hypothesise that selective antagonism of LXRα increases toxic lipid accumulation in adrenocortical cells and potentiates the adrenolytic effect of mitotane.