Mitotane is a selective inhibitor of sterol-Oacyl-transferase 1 (SOAT1), also known as ACAT1, (acyl-coenzyme A cholesterol acyltransferase).
Mitotane is a selective inhibitor of sterol-Oacyl-transferase 1 (SOAT1), also known as ACAT1, (acyl-coenzyme A cholesterol acyltransferase). Mitotane inhibition of SOAT1 in adrenocortical carcinoma cells decreased the formation of cholesteryl esters, which increased free cholesterol levels and caused endoplasmic reticulum (ER) stress, the unfolded protein response, and eventually apoptosis.
Many human diseases, including metabolic, immune and central nervous system disorders, as well as cancer, are the consequence of an alteration in lipid metabolic enzymes and their pathways. This illustrates the fundamental role played by lipids in maintaining membrane homeostasis
Mitotane is the only drug approved for treatment of the orphan disease adrenocortical carcinoma (ACC) and was recently shown to be the first clinically used drug acting through endoplasmic reticulum (ER)-stress induced by toxic lipids. Since mitotane has limited clinical
Clear cell renal cell carcinoma (ccRCC) is the most common histological type of kidney cancer and has high heterogeneity. Stratification of ccRCC is important since distinct subtypes differ in prognosis and treatment. Here, we applied a systems biology approach to
Adrenocortical carcinoma (ACC) is a rare malignancy that harbors a dismal prognosis in advanced stages. Mitotane is approved as an orphan drug for treatment of ACC and counteracts tumor growth and steroid hormone production. Despite serious adverse effects, mitotane has
Current systemic treatment options for patients with adrenocortical carcinomas (ACCs) are far from being satisfactory. DNA damage/repair mechanisms, which involve, e.g., ataxia-telangiectasia-mutated (ATM) and ataxia-telangiectasia/Rad3-related (ATR) protein signaling or ribonucleotide reductase subunits M1/M2 (RRM1/RRM2)-encoded ribonucleotide reductase (RNR) activation, commonly contribute
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