Journal article
Temozolomide: An Updated Overview of Resistance Mechanisms, Nanotechnology Advances and Clinical Applications
- Ortiz, Raúl Institute of Biopathology and Regenerative Medicine (IBIMER), Biomedical Research Centre (CIBM), University of Granada, Spain
- Perazzoli, Gloria Department of Medicine, University of Almeria, Spain
- Cabeza, Laura Institute of Biopathology and Regenerative Medicine (IBIMER), Biomedical Research Centre (CIBM), University of Granada, Spain
- Jiménez-Luna, Cristina Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, Epalinges 1066, Switzerland
- Luque, Raquel Medical Oncology Service, Virgen de las Nieves Hospital, Granada, Spain
- Prados, Jose Institute of Biopathology and Regenerative Medicine (IBIMER), Biomedical Research Centre (CIBM), University of Granada, Spain
- Melguizo, Consolación Institute of Biopathology and Regenerative Medicine (IBIMER), Biomedical Research Centre (CIBM), University of Granada, Spain
Published in:
- Current Neuropharmacology. - Bentham Science Publishers Ltd.. - 2020, vol. 18
Pharmacology (medical)
Pharmacology
Neurology
Psychiatry and Mental health
Clinical Neurology
General Medicine
English
:
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 the 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.
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 the 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.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.2174/1570159x18666200626204005
- ISSN 1570-159X
- Persistent URL
- https://folia.unifr.ch/global/documents/1864
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