The role of m6A modification in the biological functions and diseases

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Feb. 21, 2021

Abstract N 6 -methyladenosine (m6A) is the most prevalent, abundant and conserved internal cotranscriptional modification in eukaryotic RNAs, especially within higher cells. m6A modified by methyltransferases, or writers, such as METTL3/14/16, RBM15/15B, ZC3H3, VIRMA, CBLL1, WTAP, KIAA1429, and, removed demethylases, erasers, including FTO ALKBH5. It recognized m6A-binding proteins YTHDF1/2/3, YTHDC1/2 IGF2BP1/2/3 HNRNPA2B1, also known “readers”. Recent studies have shown that RNA plays essential role both physiological pathological conditions, initiation progression of different types human cancers. In this review, we discuss how methylation influences progressions hematopoietic, central nervous reproductive systems. We will mainly focus on recent progress identifying biological functions underlying molecular mechanisms methylation, its regulators downstream target genes, during cancer above propose process offer potential targets for therapy future.

Language: Английский

---

Glioma targeted therapy: insight into future of molecular approaches

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Feb. 8, 2022

Gliomas are the common type of brain tumors originating from glial cells. Epidemiologically, gliomas occur among all ages, more often seen in adults, which males susceptible than females. According to fifth edition WHO Classification Tumors Central Nervous System (WHO CNS5), standard care and prognosis can be dramatically different. Generally, circumscribed usually benign recommended early complete resection, with chemotherapy if necessary. Diffuse other high-grade according their molecule subtype slightly intractable, necessity chemotherapy. However, for glioblastoma, feasible resection followed by radiotherapy plus temozolomide define current care. Here, we discuss novel or potential targets treatment gliomas, especially IDH-wild glioblastoma. Classic such as p53 retinoblastoma (RB) pathway epidermal growth factor receptor (EGFR) gene alteration have met failure due complex regulatory network. There is ever-increasing interest immunotherapy (immune checkpoint molecule, tumor associated macrophage, dendritic cell vaccine, CAR-T), microenvironment, combination several efficacious methods. With many targeted therapy options emerging, biomarkers guiding prescription a particular also attractive. More pre-clinical clinical trials urgently needed explore evaluate feasibility corresponding effective personalized options.

Language: Английский

---

Emerging therapies for glioblastoma: current state and future directions

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: April 15, 2022

Abstract Glioblastoma (GBM) is the most common high-grade primary malignant brain tumor with an extremely poor prognosis. Given survival currently approved treatments for GBM, new therapeutic strategies are urgently needed. Advances in decades of investment basic science glioblastoma rapidly translated into innovative clinical trials, utilizing improved genetic and epigenetic profiling as well microenvironment immune system interactions. Following these encouraging findings, immunotherapy including checkpoint blockade, chimeric antigen receptor T (CAR T) cell therapy, oncolytic virotherapy, vaccine therapy have offered hope improving GBM outcomes; ongoing studies using combinatorial therapies aim minimizing adverse side-effects augmenting antitumor responses. In addition, techniques to overcome blood-brain barrier (BBB) targeted delivery being tested trials patients recurrent GBM. Here, we set forth rationales promising treating review potential novel agents, current status preclinical discuss challenges future perspectives immuno-oncology.

Language: Английский

---

Clinical practice guidelines for the management of adult diffuse gliomas

Cancer Letters, Journal Year: 2020, Volume and Issue: 499, P. 60 - 72

Published: Nov. 6, 2020

Language: Английский

---

Glioblastoma: clinical presentation, diagnosis, and management

BMJ, Journal Year: 2021, Volume and Issue: unknown, P. n1560 - n1560

Published: July 14, 2021

What you need to know1. Early symptoms of brain tumours in adults are non-specific and patients may present multiple times primary care services before they referred for investigation.Look out raised intracranial pressure (e.g.headaches exacerbated by lying down, triggered Valsalva maneuver or associated with vomiting visual disturbance), combinations (e.g.headache plus cognitive impairment, headache weakness, personality change) which progress over time.New-onset focal generalized seizures adulthood also warrant investigation a tumour.2. In signs suggestive tumour, arrange an urgent MRI head without contrast through rapid-access 'suspected cancer' pathway, when available.In suspicion pressure, same-day clinical assessment contrast-enhanced CT scan.3. Glioblastoma (GBM) is the most common cancer.Standard treatment includes maximal safe resection followed concomitant radiotherapy temozolomide (TMZ) chemotherapy then adjuvant TMZ.Disease progression expected all cases consideration further should take into account patient's performance status, tumour size, location time since first 4. Key supportive medications include corticosteroids vasogenic oedema anti-epileptic medication if occur 5. Due incurable rapidly progressive nature glioblastoma, close collaboration between multidisciplinary teams tertiary hospitals recommended.Early involvement GPs specialist community palliative can assist caregivers advance planning as well management symptoms, physical communication difficulties innate uncertainties about disease progression.

Language: Английский

---

Prognostic and Predictive Biomarkers in Gliomas

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(19), P. 10373 - 10373

Published: Sept. 26, 2021

Gliomas are the most common central nervous system tumors. New technologies, including genetic research and advanced statistical methods, revolutionize therapeutic approach to patient reveal new points of treatment options. Moreover, 2021 World Health Organization Classification Tumors Central Nervous System has fundamentally changed classification gliomas incorporated many molecular biomarkers. Given rapid progress in neuro-oncology, here we compile latest on prognostic predictive biomarkers gliomas. In adult patients, IDH mutations positive markers have greatest significance. However, CDKN2A deletion, IDH-mutant astrocytomas, is a marker highest malignancy grade. presence TERT promoter mutations, EGFR alterations, or combination chromosome 7 gain 10 loss upgrade IDH-wildtype astrocytoma glioblastoma. pediatric H3F3A alterations important which predict worse outcome. MGMT methylation clinical significance predicting responses temozolomide (TMZ). Conversely, mismatch repair defects cause hypermutation phenotype poor response TMZ. Finally, discussed liquid biopsies, promising diagnostic, prognostic, techniques, but further work needed implement these novel technologies practice.

Language: Английский

---

Glutathione S-Transferases in Cancer

Antioxidants, Journal Year: 2021, Volume and Issue: 10(5), P. 701 - 701

Published: April 29, 2021

In humans, the glutathione S-transferases (GST) protein family is composed of seven members that present remarkable structural similarity and some degree overlapping functionalities. GST proteins are crucial antioxidant enzymes regulate stress-induced signaling pathways. Interestingly, overactive a frequent feature many human cancers. Recent evidence has revealed biology most complex multifaceted these actively participate in tumorigenic processes such as cell survival, proliferation, drug resistance. Structural pharmacological studies have identified various inhibitors, molecules progressed to clinical trials for treatment cancer other diseases. this review, we discuss recent findings their roles development, contribution chemoresistance, development inhibitors treatment.

Language: Английский

---

Crosstalk between circRNAs and the PI3K/AKT signaling pathway in cancer progression

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Nov. 24, 2021

Circular RNAs (circRNAs), covalently closed noncoding RNAs, are widely expressed in eukaryotes and viruses. They can function by regulating target gene expression, linear RNA transcription protein generation. The phosphoinositide 3-kinase (PI3K)/AKT signaling pathway plays key roles many biological cellular processes, such as cell proliferation, growth, invasion, migration, angiogenesis. It also a pivotal role cancer progression. Emerging data suggest that the circRNA/PI3K/AKT axis modulates expression of cancer-associated genes thus regulates tumor Aberrant regulation circRNAs is significantly associated with clinicopathological characteristics an important functions. In this review, we summarized functions PI3K-AKT-related vitro vivo assessed their associations characteristics. We further discussed diagnosis, prognostication, treatment cancers.

Language: Английский

---

Synchronous Disintegration of Ferroptosis Defense Axis via Engineered Exosome‐Conjugated Magnetic Nanoparticles for Glioblastoma Therapy

Advanced Science, Journal Year: 2022, Volume and Issue: 9(17)

Published: May 4, 2022

Glioblastoma (GBM) is one of the most fatal central nervous system tumors and lacks effective or sufficient therapies. Ferroptosis a newly discovered method programmed cell death opens new direction for GBM treatment. However, poor blood-brain barrier (BBB) penetration, reduced tumor targeting ability, potential compensatory mechanisms hinder effectiveness ferroptosis agents during Here, novel composite therapeutic platform combining magnetic features drug delivery properties nanoparticles with BBB penetration abilities siRNA encapsulation engineered exosomes therapy presented. This can be enriched in brain under local localization angiopep-2 peptide-modified trigger transcytosis, allowing particles to cross target cells by recognizing LRP-1 receptor. Synergistic achieved combined triple actions disintegration dihydroorotate dehydrogenase glutathione peroxidase 4 defense axis Fe

Language: Английский

---

An update on the molecular biology of glioblastoma, with clinical implications and progress in its treatment

Cancer Communications, Journal Year: 2022, Volume and Issue: 42(11), P. 1083 - 1111

Published: Sept. 21, 2022

Abstract Glioblastoma multiforme (GBM) is the most aggressive and common malignant primary brain tumor. Patients with GBM often have poor prognoses, a median survival of ∼15 months. Enhanced understanding molecular biology central nervous system tumors has led to modifications in their classifications, recent which classified these into new categories made some changes nomenclature grading system. This review aims give panoramic view last 3 years’ findings glioblastoma characterization, its heterogeneity, current advances treatment. Several parameters been used achieve an accurate personalized characterization patients, including epigenetic, genetic, transcriptomic metabolic features, as well age‐ sex‐related patterns involvement several noncoding RNAs progression. Astrocyte‐like neural stem cells outer radial glial‐like from subventricular zone proposed agents involved IDH‐wildtype origin, but this remains controversial. metabolism characterized by upregulation PI3K/Akt/mTOR signaling pathway, promotion glycolytic flux, maintenance lipid storage, other features. also contributes glioblastoma's resistance conventional therapies. Tumor hallmark GBM, shown affect genetic expression, modulation pathways, immune evasion. GBM's invasion potential modulated cell‐to‐cell crosstalk within tumor microenvironment altered expressions specific genes, such ANXA2 , GBP2 FN1 PHIP GLUT3 . Nevertheless, rising number active clinical trials illustrates efforts identify targets drugs treat malignancy. Immunotherapy still relevant for research purposes, given amount ongoing based on strategy neoantigen nucleic acid‐based vaccines are gaining importance due antitumoral activity inducing response. Furthermore, there focused axis, angiogenesis, heterogeneity developing molecular‐targeted therapies against GBM. Other strategies, nanodelivery computational models, may improve drug pharmacokinetics prognosis patients

Language: Английский

---