title: The role of temozolomide in the treatment of aggressive pituitary tumors.
abstract: Pituitary tumors are amongst the most common intracranial neoplasms and are generally benign. However, some pituitary tumors exhibit clinically aggressive behavior that is characterized by tumor recurrence and continued progression despite repeated treatments with conventional surgical, radiation and medical therapies. More recently, temozolomide, a second generation oral alkylating agent, has shown therapeutic promise for aggressive pituitary adenomas and carcinomas with favorable clinical and radiographic responses. Temozolomide causes DNA damage by methylation of the O(6) position of guanine, which results in potent cytotoxic DNA adducts and consequently, tumor cell apoptosis. The degree of MGMT expression appears to be inversely related to therapeutic responsiveness to temozolomide with a significant number of temozolomide-sensitive pituitary tumors exhibiting low MGMT expression. The presence of high MGMT expression appears to mitigate the effectiveness of temozolomide and this has been used as a marker in several studies to predict the efficacy of temozolomide. Recent evidence also suggests that mutations in mismatch repair proteins such as MSH6 could render pituitary tumors resistant to temozolomide. In this article, the authors review the development of temozolomide, its biochemistry and interaction with O(6)-methylguanine-DNA methyltransferase (MGMT), its role in adjuvant treatment of aggressive pituitary neoplasms, and future works that could influence the efficacy of temozolomide therapy.
authors.affiliation: Center for Skull Base and Pituitary Surgery, Neurological Institute of New Jersey, Department of Neurological Surgery, Rutgers University, New Jersey Medical School, Suite 8100, 90 Bergen Street, Newark, NJ 07103, USA; Department of Neurological Surgery, Rutgers University, New Jersey Medical School, Newark, NJ, USA; Department of Otolaryngology-Head and Neck Surgery, Rutgers University, New Jersey Medical School, Newark, NJ, USA. Electronic address: james.liu.md@rutgers.edu.
authors.forename: James K
authors.initials: JK
authors.lastname: Liu
authors.affiliation: Department of Neurological Surgery, Rutgers University, New Jersey Medical School, Newark, NJ, USA.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Patel
authors.affiliation: Center for Skull Base and Pituitary Surgery, Neurological Institute of New Jersey, Department of Neurological Surgery, Rutgers University, New Jersey Medical School, Suite 8100, 90 Bergen Street, Newark, NJ 07103, USA; Department of Neurological Surgery, Rutgers University, New Jersey Medical School, Newark, NJ, USA; Department of Otolaryngology-Head and Neck Surgery, Rutgers University, New Jersey Medical School, Newark, NJ, USA.
authors.forename: Jean Anderson
authors.initials: JA
authors.lastname: Eloy
mesh_terms: D000236:Adenoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D045643:DNA Repair Enzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D018450:Disease Progression; D006801:Humans; D009154:Mutation / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis
chemical_list: D018906:Antineoplastic Agents, Alkylating; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide
keywords: O(6)-methylguanine-DNA methyltransferase; Pituitary adenoma; Pituitary carcinoma; Temozolomide