Temozolomide: An Updated Overview of Resistance Mechanisms, Nanotechnology Advances and Clinical Applications.

Abstract:

: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.

journal_name

Curr Neuropharmacol

authors

Ortiz R,Perazzoli G,Cabeza L,Jiménez-Luna C,Luque R,Prados J,Melguizo C

doi

10.2174/1570159X18666200626204005

subject

Has Abstract

pub_date

2020-06-26 00:00:00

eissn

1570-159X

issn

1875-6190

pii

CN-EPUB-107689

pub_type

杂志文章
  • Targeting the Autophagy/Lysosomal Degradation Pathway in Parkinson's Disease.

    abstract::Autophagy is a cellular quality control mechanism crucial for neuronal homeostasis. Defects in autophagy are critically associated with mechanisms underlying Parkinson's disease (PD), a common and debilitating neurodegenerative disorder. Autophagic dysfunction in PD can occur at several stages of the autophagy/lysosom...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章,评审

    doi:10.2174/1570159x13666151030103027

    authors: Rivero-Ríos P,Madero-Pérez J,Fernández B,Hilfiker S

    更新日期:2016-01-01 00:00:00

  • Mesenchymal stem cells for treatment of CNS injury.

    abstract::Brain and spinal cord injuries present significant therapeutic challenges. The treatments available for these conditions are largely ineffective, partly due to limitations in directly targeting the therapeutic agents to sites of pathology within the central nervous system (CNS). The use of stem cells to treat these co...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章

    doi:10.2174/157015910793358204

    authors: Azari MF,Mathias L,Ozturk E,Cram DS,Boyd RL,Petratos S

    更新日期:2010-12-01 00:00:00

  • Zinc in the Glutamatergic Theory of Depression.

    abstract::Depression is a serious psychiatric illness that affects millions of people worldwide. Weeks of antidepressant therapy are required to relieve depressive symptoms, and new drugs are still being extensively researched. The latest studies have shown that in depression, there is an imbalance between the main excitatory (...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章,评审

    doi:10.2174/1570159x13666150115220617

    authors: Mlyniec K

    更新日期:2015-01-01 00:00:00

  • Putative Involvement of Endocrine Disruptors in the Alzheimer's disease Via the Insulin-Regulated Aminopeptidase / GLUT4 Pathway.

    abstract::It has been well established that there is a connection between type II diabetes (DMTII) and Alzheimer's disease (AD). In fact, the increase in AD incidence may be an emerging complication of DMTII. Both pathologies are related to estradiol (E2) exposure on the one hand, estrogen receptors (ER) are emerging as importa...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章

    doi:10.2174/1570159X18666201111103024

    authors: Ramírez-Expósito MJ,Martínez-Martos JM,Cantón-Habas V,Carrera González MP

    更新日期:2020-11-10 00:00:00

  • Neuroprotective Effects of Exercise Treatments After Injury: The Dual Role of Neurotrophic Factors.

    abstract:BACKGROUND:Shared connections between physical activity and neuroprotection have been studied for decades, but the mechanisms underlying this effect of specific exercise were only recently brought to light. Several evidences suggest that physical activity may be a reasonable and beneficial method to improve functional ...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章,评审

    doi:10.2174/1570159X14666160330105132

    authors: Cobianchi S,Arbat-Plana A,Lopez-Alvarez VM,Navarro X

    更新日期:2017-01-01 00:00:00

  • The TNF-alpha system: functional aspects in depression, narcolepsy and psychopharmacology.

    abstract::Changes of the tumor necrosis factor-alpha (TNF-alpha) system have been shown to be involved in the development of psychiatric disorders and are additionally associated with changes in body weight as well as endocrine and metabolic changes in psychiatric patients. TNF-alpha might, for example, contribute to the pathog...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章

    doi:10.2174/157015908785777238

    authors: Berthold-Losleben M,Himmerich H

    更新日期:2008-09-01 00:00:00

  • Pathological role for exocytotic glutamate release from astrocytes in hepatic encephalopathy.

    abstract::Liver failure can lead to generalized hyperammonemia, which is thought to be the underlying cause of hepatic encephalopathy. This neuropsychiatric syndrome is accompanied by functional changes of astrocytes. These glial cells enter ammonia-induced self-amplifying cycle characterized by brain oedema, oxidative and osmo...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章

    doi:10.2174/1570159X12666140903094700

    authors: Montana V,Verkhratsky A,Parpura V

    更新日期:2014-07-01 00:00:00

  • Interferon-Related Depression: A Primer on Mechanisms, Treatment, and Prevention of a Common Clinical Problem.

    abstract:BACKGROUND:Depression is among the commonest of psychiatric disorders, and inflammatory mechanisms have been suggested to play a role in its pathophysiology. Interferons are a superfamily of proinflammatory cytokines that play a role in host defence mechanisms. Interferons are used in the treatment of a variety of auto...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章,评审

    doi:10.2174/1570159x14666160106155129

    authors: Pinto EF,Andrade C

    更新日期:2016-01-01 00:00:00

  • Growth Factors in the Pathogenesis of Retinal Neurodegeneration in Diabetes Mellitus.

    abstract::Neurodegeneration is an initial process in the development of diabetic retinopathy (DR). High quantities of glutamate, oxidative stress, induction of the renin-angiotensin system (RAS) and elevated levels of RAGE are crucial elements in the retinal neurodegeneration caused by diabetes mellitus. At least, there is emer...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章,评审

    doi:10.2174/1570159x14666160813182009

    authors: Iwona BS

    更新日期:2016-01-01 00:00:00

  • Oxidative and Nitrosative Stress and Immune-Inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS).

    abstract::Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) has been classified as a disease of the central nervous system by the WHO since 1969. Many patients carrying this diagnosis do demonstrate an almost bewildering array of biological abnormalities particularly the presence of oxidative and nitrosative stres...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章

    doi:10.2174/1570159X11666131120224653

    authors: Morris G,Maes M

    更新日期:2014-03-01 00:00:00

  • Impaired spatial memory after ketamine administration in chronic low doses.

    abstract::Ketamine is a noncompetitive antagonist of the NMDA-receptors, used as a dissociative anesthetic, presently included in the category of the psychoactive substances known as "club drugs". Ketamine administration was associated with impaired working memory and increased psychopathological symptoms, but there is a lack o...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章

    doi:10.2174/157015911795016912

    authors: Venâncio C,Magalhães A,Antunes L,Summavielle T

    更新日期:2011-03-01 00:00:00

  • Allosteric modulation of the calcium-sensing receptor.

    abstract::The calcium (Ca(2+))-sensing receptor (CaR) belongs to family C of the G-protein coupled receptors (GPCRs). The receptor is activated by physiological levels of Ca(2+) (and Mg(2+)) and positively modulated by a range of proteinogenic L-alpha-amino acids. Recently, several synthetic allosteric modulators of the recepto...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章

    doi:10.2174/157015907781695982

    authors: Jensen AA,Bräuner-Osborne H

    更新日期:2007-09-01 00:00:00

  • Natural AChE Inhibitors from Plants and their Contribution to Alzheimer's Disease Therapy.

    abstract::As acetylcholinesterase (AChE) inhibitors are an important therapeutic strategy in Alzheimer's disease, efforts are being made in search of new molecules with anti-AChE activity. The fact that naturally-occurring compounds from plants are considered to be a potential source of new inhibitors has led to the discovery o...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章

    doi:10.2174/1570159X11311040004

    authors: Murray AP,Faraoni MB,Castro MJ,Alza NP,Cavallaro V

    更新日期:2013-07-01 00:00:00

  • Recent Trends in the Management of Alzheimer's Disease: Current Therapeutic Options and Drug Repurposing Approaches.

    abstract::Alzheimer's disease is one of the most progressive forms of dementia, ultimately leading to death in aged populations. The major hallmarks of Alzheimer's disease include deposition of extracellular amyloid senile plaques and intracellular neurofibrillary tangles in brain neuronal cells. Although there are classical th...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章

    doi:10.2174/1570159X18666200128121920

    authors: Singh RK

    更新日期:2020-01-01 00:00:00

  • Clearing the brain's cobwebs: the role of autophagy in neuroprotection.

    abstract::Protein aggregates or inclusion bodies are common hallmarks of age-related neurodegenerative disorders. Why these aggregates form remains unclear. Equally debated is whether they are toxic, protective, or simple by-products. Increasing evidence, however, supports the notion that in general aggregates confer toxicity a...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章

    doi:10.2174/157015908784533897

    authors: Bossy B,Perkins G,Bossy-Wetzel E

    更新日期:2008-06-01 00:00:00

  • From Randomized Controlled Trials of Antidepressant Drugs to the Meta-Analytic Synthesis of Evidence: Methodological Aspects Lead to Discrepant Findings.

    abstract::During the last decade, several meta-analytic studies employing different methodological approaches have had inconsistent conclusions regarding antidepressant efficacy. Herein, we aim to comment on methodological aspects that may have contributed to disparate findings. We initially discuss methodological inconsistenci...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章,meta分析

    doi:10.2174/1570159x13666150630174343

    authors: Fountoulakis KN,McIntyre RS,Carvalho AF

    更新日期:2015-01-01 00:00:00

  • The benzydamine experience: a systematic review of benzydamine abuse.

    abstract:BACKGROUND:Both prescription and over-the-counter (OTC) drugs recently emerged among novel psychoactive substances (NPS) being reported as ingested for recreational purposes. Among them, benzydamine (BZY), normally prescribed as an OTC anti-inflammatory drug, is reportedly being diverted and recreationally used. OBJEC...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章

    doi:10.2174/1570159X19666210113151136

    authors: Stefania C,Andrea M,Alessio M,Mauro P,Amira G,Martin CJ,Giovanni M,Massimo DG,Fabrizio S

    更新日期:2021-01-13 00:00:00

  • Pediatric Mania: The Controversy between Euphoria and Irritability.

    abstract::Pediatric Bipolar Disorder (BD) is a highly morbid pediatric psychiatric disease, consistently associated with family psychiatric history of mood disorders and associated with high levels of morbidity and disability and with a great risk of suicide. While there is a general consensus on the symptomatology of depressio...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章,评审

    doi:10.2174/1570159X14666160607100403

    authors: Serra G,Uchida M,Battaglia C,Casini MP,De Chiara L,Biederman J,Vicari S,Wozniak J

    更新日期:2017-04-01 00:00:00

  • Autoimmune channelopathies of the nervous system.

    abstract::Ion channels are complex transmembrane proteins that orchestrate the electrical signals necessary for normal function of excitable tissues, including the central nervous system, peripheral nerve, and both skeletal and cardiac muscle. Progress in molecular biology has allowed cloning and expression of genes that encode...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章

    doi:10.2174/157015911796557966

    authors: Kleopa KA

    更新日期:2011-09-01 00:00:00

  • Mst1: Function and Mechanism in Brain and Myocardial Ischemia Reperfusion Injury.

    abstract::Mammalian STE20-like kinase-1 (Mst1) is a generally expressed apoptosis-promoting kinase and a key bridgebuilder of apoptotic signaling in the etiology of tissue injury. Despite the fact that the biological function of Mst1 and its role in the cell's signalling network have yet to be determined, however, there is a lo...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章,评审

    doi:10.2174/1570159X16666180516095949

    authors: Li D,Ni H,Rui Q,Gao R,Chen G

    更新日期:2018-01-01 00:00:00

  • The Role of mGlu Receptors in Hippocampal Plasticity Deficits in Neurological and Psychiatric Disorders: Implications for Allosteric Modulators as Novel Therapeutic Strategies.

    abstract::Long-term potentiation (LTP) and long-term depression (LTD) are two distinct forms of synaptic plasticity that have been extensively characterized at the Schaffer collateral-CA1 (SCCA1) synapse and the mossy fiber (MF)-CA3 synapse within the hippocampus, and are postulated to be the molecular underpinning for several ...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章,评审

    doi:10.2174/1570159x13666150421003225

    authors: Senter RK,Ghoshal A,Walker AG,Xiang Z,Niswender CM,Conn PJ

    更新日期:2016-01-01 00:00:00

  • Potential effects of cannabidiol as a wake-promoting agent.

    abstract::Over the last decades, the scientific interest in chemistry and pharmacology of cannabinoids has increased. Most attention has focused on ∆(9)-tetrahydrocannabinol (∆(9)-THC) as it is the psychoactive constituent of Cannabis sativa (C. sativa). However, in previous years, the focus of interest in the second plant cons...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章

    doi:10.2174/1570159X11666131204235805

    authors: Murillo-Rodríguez E,Sarro-Ramírez A,Sánchez D,Mijangos-Moreno S,Tejeda-Padrón A,Poot-Aké A,Guzmán K,Pacheco-Pantoja E,Arias-Carrión O

    更新日期:2014-05-01 00:00:00

  • Traumatic Brain Injury: A Forensic Approach: A Literature Review.

    abstract::Traumatic brain injury (TBI) is the principal cause of invalidity and death in the population under 45 years of age worldwide. This mini-review aims to systematize the forensic approach in neuropathological studies, highlighting the proper elements to be noted during external, radiological, autoptical, and histologica...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章

    doi:10.2174/1570159X17666191101123145

    authors: Bertozzi G,Maglietta F,Sessa F,Scoto E,Cipolloni L,Di Mizio G,Salerno M,Pomara C

    更新日期:2020-01-01 00:00:00

  • Recent Advances in Pathophysiology of Traumatic Brain Injury.

    abstract:BACKGROUND:Traumatic brain injury (TBI) constitutes the primary reason for mortality and morbidity in persons worldwide below 45 years of age. 1.7 million Traumatic events occur yearly in the United States alone, considering for 50,000 deaths. In severe traumatic brain injury sufferers, a considerable achievement attai...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章,评审

    doi:10.2174/1570159X15666170613083606

    authors: Kaur P,Sharma S

    更新日期:2018-01-01 00:00:00

  • Proteomic analysis of glioma chemoresistance.

    abstract::Malignant glioma is the most common and destructive form of primary brain tumor. Along with surgery and radiation, chemotherapy remains as the major treatment modality. The emergence of drug resistance, however, often leads to a therapeutic failure in the treatment of glioma, precluding long-term survival of the patie...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章

    doi:10.2174/157015912799362733

    authors: Suk K

    更新日期:2012-03-01 00:00:00

  • Neuronal and Extraneuronal Nicotinic Acetylcholine Receptors.

    abstract::Neuronal nicotinic acetylcholine receptors (nAChRs) belong to a super-family of Cysloop ligand-gated ion channels that respond to endogenous acetylcholine (ACh) or other cholinergic ligands. These receptors are also the targets of drugs such as nicotine (the main addictive agent delivered by cigarette smoke) and are i...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章,评审

    doi:10.2174/1570159X15666170912110450

    authors: Zoli M,Pucci S,Vilella A,Gotti C

    更新日期:2018-01-01 00:00:00

  • An Overview of the Heterogeneity of Major Depressive Disorder: Current Knowledge and Future Prospective.

    abstract::Major depressive disorder (MDD) is estimated to impose maximum debilitating effects on the society by 2030, with its critical effects on health, functioning, quality of life and concomitant high levels of morbidity and mortality. Yet, the disease is inadequately understood, diagnosed and treated. Moreover, with the re...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章,评审

    doi:10.2174/1570159X17666191001142934

    authors: Athira KV,Bandopadhyay S,Samudrala PK,Naidu VGM,Lahkar M,Chakravarty S

    更新日期:2020-01-01 00:00:00

  • Nanotechnology Applications for Diffuse Intrinsic Pontine Glioma.

    abstract::Diffuse intrinsic pontine gliomas (DIPGs) are invariably fatal tumors found in the pons of elementary school aged children. These tumors are grade II-IV gliomas, with a median survival of less than 1 year from diagnosis when treated with standard of care (SOC) therapy. Nanotechnology may offer therapeutic options for ...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章,评审

    doi:10.2174/1570159x14666160223121002

    authors: Bredlau AL,Dixit S,Chen C,Broome AM

    更新日期:2017-01-01 00:00:00

  • Role of wnt signaling in the control of adult hippocampal functioning in health and disease: therapeutic implications.

    abstract::It is well recognized the role of the Wnt pathway in many developmental processes such as neuronal maturation, migration, neuronal connectivity and synaptic formation. Growing evidence is also demonstrating its function in the mature brain where is associated with modulation of axonal remodeling, dendrite outgrowth, s...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章

    doi:10.2174/1570159X11311050001

    authors: Ortiz-Matamoros A,Salcedo-Tello P,Avila-Muñoz E,Zepeda A,Arias C

    更新日期:2013-09-01 00:00:00

  • Use of Push-Pull Superfusion Technique for Identifying Neurotransmitters Involved in Brain Functions: Achievements and Perspectives.

    abstract::The push-pull superfusion technique (PPST) is a procedure for in vivo examination of transmitter release in distinct brain areas. This technique allows to investigate dynamics of transmitter release both under normal and experimentally evoked conditions. The PPST can be modified so that it is possible to determine rel...

    journal_title:Current neuropharmacology

    pub_type: 杂志文章,评审

    doi:10.2174/1570159x13666150722233149

    authors: Kraus MM,Philippu A

    更新日期:2015-01-01 00:00:00