Current Understanding, Unresolved Issues, and Future Directions

Luis V. Syro1*, Fabio Rotondo2, Mauricio Camargo3, Leon D. Ortiz4, Carlos A. Serna5 and Kalman Kovacs2
  • 1Department of Neurosurgery, Hospital Pablo Tobon Uribe and Clinica Medellin, Medellin, Colombia
  • 2Department of Laboratory Medicine, Division of Pathology, St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada
  • 3Genetics, Regeneration and Cancer Laboratory, Universidad de Antioquia, Medellin, Colombia
  • 4Division of Neuro-oncology, Instituto de Cancerología, Clinica Las Americas, Pharmacogenomics, Universidad CES, Medellin, Colombia
  • 5Laboratorio de Patologia y Citologia Rodrigo Restrepo, Department of Pathology, Clinica Las Américas, Universidad CES, Medellin, Colombia
Temozolomide, an alkylating agent, initially used in the treatment of gliomas was expanded to include pituitary tumors in 2006. After 12 years of use, temozolomide has shown a notable advancement in pituitary tumor treatment with a remarkable improvement rate in the 5-year overall survival and 5-year progression-free survival in both aggressive pituitary adenomas and pituitary carcinomas. In this paper, we review the mechanism of action of temozolomide as alkylating agent, its interaction with deoxyribonucleic acid repair systems, therapeutic effects in pituitary tumors, unresolved issues, and future directions relating to new possibilities of targeted therapy.

Introduction

Since its development, temozolomide (TMZ), a monofunctional alkylating agent, has shown remarkable efficacy in the treatment of a variety of solid tumors and it has become an essential component of adjuvant therapy for the most frequent adult brain tumor type, glioblastoma multiforme (GBM) (1, 2). Its unique chemical structure and pharmacokinetic properties confer distinctive advantages over other alkylating agents. In 2006, TMZ began to be used for the treatment of aggressive pituitary adenomas and pituitary carcinomas (35). In this paper, we review the mechanism of action of TMZ, the deoxyribonucleic acid (DNA) repair systems triggered after its administration, the current understanding of TMZ activity, and the unresolved issues of its clinical use in pituitary tumors.

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