There have been several reports of the use of temozolomide (TMZ) in the treatment of malignant pituitary adenomas. The explanation for the response of malignant pituitary adenomas to TMZ is speculative, but it is conceivable that, like TMZ-responsive gliomas, responsive malignant pituitary adenomas harbor a methylated O6-methyl-guanine-DNA methyltransferase (MGMT) gene promoter. In a variety of human tumors, MGMT gene promoter hypermethylation has been associated with epigenetic inactivation of the gene and subsequent loss of the MGMT protein, which plays an important role in the repair of DNA damage, including that induced by alkylating agents such as TMZ. In therapeutic trials of radiation and TMZ in patients with malignant gliomas, patients whose tumors contained a hypermethylated MGMT gene promoter had a significantly longer survival time than patients whose tumors had an unmethylated MGMT gene promoter. Analysis of the methylation status of the MGMT promoter in a series of patients with invasive pituitary adenomas treated with TMZ would allow confirmation of this hypothesis. Immunohistochemical study of MGMT is also useful for the prediction of the effectiveness of TMZ for malignant pituitary adenomas. TMZ is highly recommended for patients with malignant pituitary adenomas that are resistant to conventional therapies. Nevertheless, there are some tumors unresponsive to TMZ. Further investigation will be required to elucidate the mechanism concerning the chemosensitivity to TMZ in malignant pituitary tumors.
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