Investigating the role of the Liver X Receptor in Potentiating Mitotane Therapy in Adrenocortical Carcinoma
Accepted version
Peer-reviewed
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Repository DOI
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Authors
Warde, K
Donlon, PT
Schoenmakers, Erik https://orcid.org/0000-0003-0674-8282
Gurnell, Mark https://orcid.org/0000-0001-5745-6832
Dennedy, MC
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.
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Keywords
Journal Title
IRISH JOURNAL OF MEDICAL SCIENCE
Conference Name
Irish Endocrine Society
Journal ISSN
0021-1265
1863-4362
1863-4362
Volume Title
187
Publisher
Publisher DOI
Sponsorship
Wellcome Trust (095564/Z/11/Z)