scholarly journals Molecular Mechanisms of Drug Resistance in Glioblastoma

2021 ◽  
Vol 22 (12) ◽  
pp. 6385
Author(s):  
Maya A. Dymova ◽  
Elena V. Kuligina ◽  
Vladimir A. Richter
Keyword(s):  
Drug Resistance ◽  
Brain Tumor ◽  
Molecular Mechanisms ◽  
Primary Brain Tumor ◽  
Therapeutic Resistance ◽  
Molecular Characteristics ◽  
Blood Brain ◽  
Conventional Radiation ◽  
The Brain ◽  
Made In

Glioblastoma multiforme (GBM) is the most common and fatal primary brain tumor, is highly resistant to conventional radiation and chemotherapy, and is not amenable to effective surgical resection. The present review summarizes recent advances in our understanding of the molecular mechanisms of therapeutic resistance of GBM to already known drugs, the molecular characteristics of glioblastoma cells, and the barriers in the brain that underlie drug resistance. We also discuss the progress that has been made in the development of new targeted drugs for glioblastoma, as well as advances in drug delivery across the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB).

scholarly journals ABC Transporters at the Blood–Brain Interfaces, Their Study Models, and Drug Delivery Implications in Gliomas

Pharmaceutics ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 20 ◽  
Author(s):  
David Gomez-Zepeda ◽  
Méryam Taghi ◽  
Jean-Michel Scherrmann ◽  
Xavier Decleves ◽  
Marie-Claude Menet
Keyword(s):  
Drug Delivery ◽  
Drug Resistance ◽  
Anticancer Drugs ◽  
Abc Transporters ◽  
Drug Transport ◽  
De Novo ◽  
Molecular Characteristics ◽  
Primary Tumors ◽  
Blood Brain ◽  
The Brain

Drug delivery into the brain is regulated by the blood–brain interfaces. The blood–brain barrier (BBB), the blood–cerebrospinal fluid barrier (BCSFB), and the blood–arachnoid barrier (BAB) regulate the exchange of substances between the blood and brain parenchyma. These selective barriers present a high impermeability to most substances, with the selective transport of nutrients and transporters preventing the entry and accumulation of possibly toxic molecules, comprising many therapeutic drugs. Transporters of the ATP-binding cassette (ABC) superfamily have an important role in drug delivery, because they extrude a broad molecular diversity of xenobiotics, including several anticancer drugs, preventing their entry into the brain. Gliomas are the most common primary tumors diagnosed in adults, which are often characterized by a poor prognosis, notably in the case of high-grade gliomas. Therapeutic treatments frequently fail due to the difficulty of delivering drugs through the brain barriers, adding to diverse mechanisms developed by the cancer, including the overexpression or expression de novo of ABC transporters in tumoral cells and/or in the endothelial cells forming the blood–brain tumor barrier (BBTB). Many models have been developed to study the phenotype, molecular characteristics, and function of the blood–brain interfaces as well as to evaluate drug permeability into the brain. These include in vitro, in vivo, and in silico models, which together can help us to better understand their implication in drug resistance and to develop new therapeutics or delivery strategies to improve the treatment of pathologies of the central nervous system (CNS). In this review, we present the principal characteristics of the blood–brain interfaces; then, we focus on the ABC transporters present on them and their implication in drug delivery; next, we present some of the most important models used for the study of drug transport; finally, we summarize the implication of ABC transporters in glioma and the BBTB in drug resistance and the strategies to improve the delivery of CNS anticancer drugs.

Glioblastoma therapeutic approaches were established utilizing contemporary discoveries in delivering medicines to the brain as smart nanoparticles for focused therapy

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Brain Tumor ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Treatment Options ◽  
Brain Targeting ◽  
Cns Drug Delivery ◽  
Blood Brain ◽  
Medication Delivery ◽  
Prospective Application ◽  
The Brain

The blood-brain barrier (primary) and the blood-brain tumor barrier (secondary) are the main barriers for Glioblastoma (GBM) treatment options. Brain design is connected to a critical barrier that restricts medicine delivery to a specific brain region, leaving the rest of the brain without therapeutic chemicals. This requires moving to a different treatment strategy to reach effective therapeutic concentration in brain tumor tissue. Due to more accurate controlled release of medication to the affected area, a continual shift from standard treatment to targeted administration of medication to the brain is attracting more attention these days. GBM's therapeutic approach was established utilizing contemporary discoveries in delivering medicines to the brain as smart nanoparticles for focused therapy. Better knowledge of molecular mechanisms involved in brain targeting and receptor-based therapeutic potential can boost the therapy results. Nonetheless, the most promising technology is still under development, and continual attempts to infer the fundamental process involved in medication delivery will assist hasten nanoparticles' translation into clinical application. Furthermore, numerous complex nanoparticles, including multifunctional smart nanoparticles, have been created to overcome such challenges for CNS drug delivery and their prospective application has been clinically demonstrated or is in the trial phase.

scholarly journals Friend or Foe: Paradoxical Roles of Autophagy in Gliomagenesis

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1411
Author(s):  
Don Carlo Ramos Batara ◽  
Moon-Chang Choi ◽  
Hyeon-Uk Shin ◽  
Hyunggee Kim ◽  
Sung-Hak Kim
Keyword(s):  
Brain Tumor ◽  
Glioblastoma Multiforme ◽  
Cancer Biology ◽  
Molecular Mechanisms ◽  
Primary Brain Tumor ◽  
Molecular Target ◽  
Therapeutic Strategies ◽  
Homeostatic Mechanism ◽  
Cellular Context ◽  
Cellular Components

Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor in adults, with a poor median survival of approximately 15 months after diagnosis. Despite several decades of intensive research on its cancer biology, treatment for GBM remains a challenge. Autophagy, a fundamental homeostatic mechanism, is responsible for degrading and recycling damaged or defective cellular components. It plays a paradoxical role in GBM by either promoting or suppressing tumor growth depending on the cellular context. A thorough understanding of autophagy’s pleiotropic roles is needed to develop potential therapeutic strategies for GBM. In this paper, we discussed molecular mechanisms and biphasic functions of autophagy in gliomagenesis. We also provided a summary of treatments for GBM, emphasizing the importance of autophagy as a promising molecular target for treating GBM.

scholarly journals PIWI-interacting RNAs and PIWI proteins in glioma: molecular pathogenesis and role as biomarkers

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Omid Reza Tamtaji ◽  
Mohammad Behnam ◽  
Mohammad Ali Pourattar ◽  
Michael R. Hamblin ◽  
Maryam Mahjoubin-Tehran ◽  
...  
Keyword(s):  
Risk Factors ◽  
Brain Tumor ◽  
Health Problem ◽  
Molecular Mechanisms ◽  
Primary Brain Tumor ◽  
Epigenetic Mechanisms ◽  
Major Health Problem ◽  
Major Health ◽  
The World ◽  
Cellular Pathways

AbstractGlioma is the most common primary brain tumor, and is a major health problem throughout the world. Today, researchers have discovered many risk factors that are associated with the initiation and progression of gliomas. Studies have shown that PIWI-interacting RNAs (piRNAs) and PIWI proteins are involved in tumorigenesis by epigenetic mechanisms. Hence, it seems that piRNAs and PIWI proteins may be potential prognostic, diagnostic or therapeutic biomarkers in the treatment of glioma. Previous studies have demonstrated a relationship between piRNAs and PIWI proteins and some of the molecular and cellular pathways in glioma. Here, we summarize recent evidence and evaluate the molecular mechanisms by which piRNAs and PIWI proteins are involved in glioma.

scholarly journals Novel delivery methods bypassing the blood-brain and blood-tumor barriers

2015 ◽  
Vol 38 (3) ◽  
pp. E10 ◽  
Author(s):  
Benjamin K. Hendricks ◽  
Aaron A. Cohen-Gadol ◽  
James C. Miller
Keyword(s):  
Primary Brain Tumor ◽  
Pathological Process ◽  
Therapeutic Interventions ◽  
Delivery Methods ◽  
Ongoing Research ◽  
Functional Capabilities ◽  
Blood Brain ◽  
Natural Protection ◽  
The Brain ◽  
Brain Homeostasis

Glioblastoma (GBM) is the most common primary brain tumor and carries a grave prognosis. Despite years of research investigating potentially new therapies for GBM, the median survival rate of individuals with this disease has remained fairly stagnant. Delivery of drugs to the tumor site is hampered by various barriers posed by the GBM pathological process and by the complex physiology of the blood-brain and blood–cerebrospinal fluid barriers. These anatomical and physiological barriers serve as a natural protection for the brain and preserve brain homeostasis, but they also have significantly limited the reach of intraparenchymal treatments in patients with GBM. In this article, the authors review the functional capabilities of the physical and physiological barriers that impede chemotherapy for GBM, with a specific focus on the pathological alterations of the blood-brain barrier (BBB) in this disease. They also provide an overview of current and future methods for circumventing these barriers in therapeutic interventions. Although ongoing research has yielded some potential options for future GBM therapies, delivery of chemotherapy medications across the BBB remains elusive and has limited the efficacy of these medications.

scholarly journals Opportunities and challenges of glioma organoids

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiangdong Xu ◽  
Lingfei Li ◽  
Linting Luo ◽  
Lingling Shu ◽  
Xiaoli Si ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Animal Models ◽  
3D Structure ◽  
Primary Brain Tumor ◽  
Surgical Removal ◽  
Human Tissues ◽  
Cell Models ◽  
Cell Dynamics ◽  
Research Platform ◽  
The Brain

AbstractGlioma is the most common primary brain tumor and its prognosis is poor. Despite surgical removal, glioma is still prone to recurrence because it grows rapidly in the brain, is resistant to chemotherapy, and is highly aggressive. Therefore, there is an urgent need for a platform to study the cell dynamics of gliomas in order to discover the characteristics of the disease and develop more effective treatments. Although 2D cell models and animal models in previous studies have provided great help for our research, they also have many defects. Recently, scientific researchers have constructed a 3D structure called Organoids, which is similar to the structure of human tissues and organs. Organoids can perfectly compensate for the shortcomings of previous glioma models and are currently the most suitable research platform for glioma research. Therefore, we review the three methods currently used to establish glioma organoids. And introduced how they play a role in the diagnosis and treatment of glioma. Finally, we also summarized the current bottlenecks and difficulties encountered by glioma organoids, and the current efforts to solve these difficulties.

scholarly journals Acanthosis nigricans and the sign of leser-trelat associated with primary brain tumor: Case report

2008 ◽  
Vol 16 (3-4) ◽  
pp. 81-83
Author(s):  
Slobodan Stojanovic ◽  
Pavle Jeremic ◽  
Mirjana Poljacki
Keyword(s):  
Brain Tumor ◽  
Acanthosis Nigricans ◽  
Neck Region ◽  
Primary Brain Tumor ◽  
Skin Tumors ◽  
Low Grade ◽  
Seborrheic Keratosis ◽  
Skin Changes ◽  
Clinical Changes ◽  
The Brain

The authors present a case of a female patient a 26-year old pensioner from Zmajevo, who developed skin changes in the neck region, armpits and groins, as well as in submammal folds during the 10 years period. The changes include dark-brown hyper?pigmentation associated with sudden eruption of a large number of benign skin tumors and dark-brown seborrheic keratosis on trunk and extremities. In 1998, after magnetic resonance imaging, primary brain tumor of astrocytoma type with low grade of malignity was discovered in thalamus region. The patient developed the above-mentioned skin changes since then. According to neurosurgical findings, the brain tumor is inoperable, so skin changes are persistent and stationary. Clinical changes correspond to paraneoplastic form of acanthosis nigricans. Numerous skin tumors histopathologically match seborrheic keratosis and reveal the clinical features of the sign of Leser-Trelat. It is interesting that in the same patient there are both, obligatory and optional, paraneoplastic dermatoses associated with malignant brain tumor.

scholarly journals The CNS and the Brain Tumor Microenvironment: Implications for Glioblastoma Immunotherapy

2020 ◽  
Vol 21 (19) ◽  
pp. 7358
Author(s):  
Fiona A. Desland ◽  
Adília Hormigo
Keyword(s):  
T Cells ◽  
Brain Tumor ◽  
Tumor Microenvironment ◽  
Immune Modulation ◽  
Primary Brain Tumor ◽  
Cellular Heterogeneity ◽  
Checkpoint Molecule ◽  
Engineered T Cells ◽  
Immunosuppressive Tumor Microenvironment ◽  
The Brain

Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. Its aggressive nature is attributed partly to its deeply invasive margins, its molecular and cellular heterogeneity, and uniquely tolerant site of origin—the brain. The immunosuppressive central nervous system (CNS) and GBM microenvironments are significant obstacles to generating an effective and long-lasting anti-tumoral response, as evidenced by this tumor’s reduced rate of treatment response and high probability of recurrence. Immunotherapy has revolutionized patients’ outcomes across many cancers and may open new avenues for patients with GBM. There is now a range of immunotherapeutic strategies being tested in patients with GBM that target both the innate and adaptive immune compartment. These strategies include antibodies that re-educate tumor macrophages, vaccines that introduce tumor-specific dendritic cells, checkpoint molecule inhibition, engineered T cells, and proteins that help T cells engage directly with tumor cells. Despite this, there is still much ground to be gained in improving the response rates of the various immunotherapies currently being trialed. Through historical and contemporary studies, we examine the fundamentals of CNS immunity that shape how to approach immune modulation in GBM, including the now revamped concept of CNS privilege. We also discuss the preclinical models used to study GBM progression and immunity. Lastly, we discuss the immunotherapeutic strategies currently being studied to help overcome the hurdles of the blood–brain barrier and the immunosuppressive tumor microenvironment.

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