What is the mechanism of action of mitotane? Is it a targeted drug or a chemotherapy drug?

Mitotane is a drug used to treat adrenocortical cancer (ACC). Its main mechanism of action is to inhibit the function and proliferation of adrenocortical cells. Mitotane selectively damages the mitochondria of adrenocortical cells and interferes with their synthesis of steroid hormones, thereby reducing the secretion of cortisol and other adrenal hormones. This effect not only affects cancerous adrenal tissue, but also has a certain inhibitory effect on normal adrenal cells, so it may lead to adrenal insufficiency.

From a molecular level, mitotane can change the metabolic process of cholesterol, inhibit the conversion of cholesterol into corticosteroids, and induce apoptosis of adrenal cells. In addition, the metabolites of mitotane can accumulate in adrenal tissue and further enhance cytotoxicity, making it a targeted cytotoxic drug. However, its effects are broader and different from traditional precision targeted drugs.

In terms of drug classification, mitotane is a cytotoxic drug and is usually classified as a chemotherapy drug rather than a targeted drug in the strict sense. Although it has certain selectivity for adrenocortical cancer, because it widely affects the synthesis of steroid hormones and has toxic effects on normal adrenal cells, it is closer to the classic chemotherapy mechanism rather than targeted therapy for specific gene mutations or proteins.

Because the mechanism of action of mitotane involves the inhibition of steroid hormones, patients may develop adrenal insufficiency during use and require hormone replacement therapy. In addition, the drug has a slow onset of action and takes weeks to months to reach stable blood concentrations. Therefore, blood levels and endocrine function need to be closely monitored during treatment to adjust the dose and manage potential adverse reactions.