Plasma-guided mitotane for the treatment of adrenocortical carcinoma:adjuvant care to advanced diseaseOA
Adrenocortical carcinoma(ACC)is a rare and highly aggressive endocrine malignancy with limited therapeutic options and a substantial risk of postoperative recurrence.Mitotane remains the only US Food and Drug Administration(USFDA)and the European Medicines Agency(EMA)approved agent specifically for ACC.Its antitumor activity involves disruption of cholesterol trafficking,inhibition of steroidogenic enzymes,and mitochondrial dysfunction,leading to selective cytotoxicity in adrenocortical cells.Current evidence indicates that maintaining therapeutic plasma concentrations between 14 mg/L and 20 mg/L is critical for clinical benefit,underscoring the importance of therapeutic drug monitoring.Mitotane is used in both adjuvant and advanced disease settings;however,its highly variable pharmacokinetics,broad endocrine disruptions,and frequent gastrointestinal and neurological toxicities require individualized dosing strategies and comprehensive supportive care.This review summarizes recent advances in the understanding of mitotane’s molecular mechanisms,pharmacogenetic determinants,clinical efficacy,and adverse-effect profile,with an emphasis on laboratory monitoring and practical considerations for optimizing treatment in ACC.
Lu-ming Wu;Ting-wei Su;Lei Jiang;Wei-wei Zhou;Yi-ran Jiang;Cui Zhang;Xu Zhong;Wei-qing Wang
Department of Endocrine and Metabolic Diseases,Shanghai Institute of Endocrine and Metabolic Diseases,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China National Clinical Research Center for Metabolic Diseases(Shanghai),Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China,National Research Center for Translational Medicine,Shanghai Key Laboratory for Endocrine Tumor,State Key Laboratory of Medical Genomics,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,ChinaDepartment of Endocrine and Metabolic Diseases,Shanghai Institute of Endocrine and Metabolic Diseases,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China National Clinical Research Center for Metabolic Diseases(Shanghai),Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China,National Research Center for Translational Medicine,Shanghai Key Laboratory for Endocrine Tumor,State Key Laboratory of Medical Genomics,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,ChinaDepartment of Endocrine and Metabolic Diseases,Shanghai Institute of Endocrine and Metabolic Diseases,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China National Clinical Research Center for Metabolic Diseases(Shanghai),Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China,National Research Center for Translational Medicine,Shanghai Key Laboratory for Endocrine Tumor,State Key Laboratory of Medical Genomics,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,ChinaDepartment of Endocrine and Metabolic Diseases,Shanghai Institute of Endocrine and Metabolic Diseases,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China National Clinical Research Center for Metabolic Diseases(Shanghai),Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China,National Research Center for Translational Medicine,Shanghai Key Laboratory for Endocrine Tumor,State Key Laboratory of Medical Genomics,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,ChinaDepartment of Endocrine and Metabolic Diseases,Shanghai Institute of Endocrine and Metabolic Diseases,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China National Clinical Research Center for Metabolic Diseases(Shanghai),Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China,National Research Center for Translational Medicine,Shanghai Key Laboratory for Endocrine Tumor,State Key Laboratory of Medical Genomics,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,ChinaDepartment of Endocrine and Metabolic Diseases,Shanghai Institute of Endocrine and Metabolic Diseases,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China National Clinical Research Center for Metabolic Diseases(Shanghai),Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China,National Research Center for Translational Medicine,Shanghai Key Laboratory for Endocrine Tumor,State Key Laboratory of Medical Genomics,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,ChinaDepartment of Endocrine and Metabolic Diseases,Shanghai Institute of Endocrine and Metabolic Diseases,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China National Clinical Research Center for Metabolic Diseases(Shanghai),Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China,National Research Center for Translational Medicine,Shanghai Key Laboratory for Endocrine Tumor,State Key Laboratory of Medical Genomics,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,ChinaDepartment of Endocrine and Metabolic Diseases,Shanghai Institute of Endocrine and Metabolic Diseases,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China National Clinical Research Center for Metabolic Diseases(Shanghai),Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China,National Research Center for Translational Medicine,Shanghai Key Laboratory for Endocrine Tumor,State Key Laboratory of Medical Genomics,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China
医药卫生
MitotaneAdrenocortical carcinoma(ACC)SteroidogenesisCholesterol metabolism
《LabMed Discovery》 2025 (4)
P.41-47,7
supported by the National Natural Science Foundation of China(Nos.82403817 and 82170797)Shanghai Municipal Health Commission,China(Nos.20224Y0088,2022YQ021 and 202440098)Shanghai Municipal Science and Technology Commission,China(No.24QA2705200)Shanghai Shenkang Hospital Development Center,China(Nos.SHDC2024CRI081,SHDC22022301,SHDC22025304 and SHDC2025CCS022).
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