RT Journal Article
T1 Temozolomide: An Updated Overview of Resistance Mechanisms, Nanotechnology Advances and Clinical Applications.
A1 Ortiz, Raúl
A1 Perazzoli, Gloria
A1 Cabeza, Laura
A1 Jiménez-Luna, Cristina
A1 Luque, Raquel
A1 Prados, Jose
A1 Melguizo, Consolación
K1 Alkylating agents
K1 cancer
K1 chemotherapy
K1 clinical trials
K1 drug resistance
K1 nanoparticles
AB Temozolomide (TMZ), an oral alkylating prodrug which delivers a methyl group to purine bases of DNA (O6-guanine; N7-guanine and N3-adenine), is frequently used together with radiotherapy as part of the first-line treatment of high-grade gliomas. The main advantages are its high oral bioavailability (almost 100% although the concentration found in the cerebrospinal fluid was approximately 20% of the plasma concentration of TMZ), its lipophilic properties, and small size that confer the ability to cross the blood-brain barrier. Furthermore, this agent has demonstrated activity not only in brain tumors but also in a variety of solid tumors. However, conventional therapy using surgery, radiation, and TMZ in glioblastoma results in a median patient survival of 14.6 months. Treatment failure has been associated with tumor drug resistance. This phenomenon has been linked to the expression of O6-methylguanine-DNA methyltransferase, but the mismatch repair system and the presence of cancer stem-like cells in tumors have also been related to TMZ resistance. The understanding of these mechanisms is essential for the development of new therapeutic strategies in the clinical use of TMZ, including the use of nanomaterial delivery systems and the association with other chemotherapy agents. The aim of this review is to summarize the resistance mechanisms of TMZ and the current advances to improve its clinical use.
YR 2021
FD 2021
LK http://hdl.handle.net/10668/15832
UL http://hdl.handle.net/10668/15832
LA en
DS RISalud
RD Apr 7, 2025