Adrenocortical carcinomas (ACCs) are rare and aggressive malignancies of adrenal cortex, associated with largely unknown mechanisms of biological development and poor prognosis. Currently, mitotane is the sole approved drug for treating advanced adrenocortical carcinomas (ACCs) and is being utilized more frequently as postoperative adjuvant therapy. Although it is understood that mitotane targets the adrenal cortex and disrupts steroid production, its precise mechanism of action requires further exploration. Additionally, mitotane affects cytochrome P450 enzymes, causes the depolarization of mitochondrial membranes, and leads to an accumulation of free cholesterol, ultimately resulting in cell death. Many patients treated with mitotane develop disease progression over time, underlying the need to understand the mechanisms of primary and acquired resistance. In this manuscript, we provide an overview on the intracellular mechanisms of action of mitotane, exploring data regarding predictive factors of response and evidence associated with the development of primary and acquired resistance mechanisms. In this discussion, mitotane is considered a real target therapy.
肾上腺皮质癌是一种罕见且具有侵袭性的肾上腺皮质恶性肿瘤，其生物学发展机制尚不明确，预后较差。目前，米托坦是唯一获批用于治疗晚期肾上腺皮质癌的药物，并越来越多地用于术后辅助治疗。尽管已知米托坦作用于肾上腺皮质并干扰类固醇生成，但其确切作用机制仍需进一步探索。此外，米托坦影响细胞色素P450酶，引起线粒体膜去极化，并导致游离胆固醇积聚，最终导致细胞死亡。许多接受米托坦治疗的患者随时间推移出现疾病进展，这凸显了理解原发性和获得性耐药机制的必要性。本文综述了米托坦的细胞内作用机制，探讨了有关治疗反应预测因素的数据，以及与原发性及获得性耐药机制发展相关的证据。在此讨论中，米托坦被视为一种真正的靶向治疗药物。
A Review on Mitotane: A Target Therapy in Adrenocortical Carcinoma
肿瘤(癌症)患者之家