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      An update of advanced nanoplatforms for Glioblastoma Multiforme Management

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          Abstract

          Glioblastoma multiforme (GBM) is a very aggressive and heterogeneous glioma. Currently, GBM is treated with a combination of surgery, radiotherapy, chemotherapy (e.g. temozolamide) and Tumour Treating Fields. Unfortunately, the mean survival is still around 15 months. This poor prognosis is associated with therapy resistance, tumor recurrence, and limited delivery of drugs due to the blood-brain barrier nature. Nanomedicine, the application of nanotechnology to medicine, has revolutionized many health fields, specifically cancer diagnosis and treatment. This review explores the particularities of different nanosystems (i.e., superparamagnetic, polymeric and gold nanoparticles, and liposomes) as well as how they can be applied to the treatment and diagnosis of GBM. As described, the most of the cited examples are on the preclinical phase; however, positive results were obtained and thus, the distance to achieve an effective treatment is shorter every day.

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          The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary.

          Paul Kleihues, Otmar D. Wiestler, Guido Reifenberger … (2016)
          The 2016 World Health Organization Classification of Tumors of the Central Nervous System is both a conceptual and practical advance over its 2007 predecessor. For the first time, the WHO classification of CNS tumors uses molecular parameters in addition to histology to define many tumor entities, thus formulating a concept for how CNS tumor diagnoses should be structured in the molecular era. As such, the 2016 CNS WHO presents major restructuring of the diffuse gliomas, medulloblastomas and other embryonal tumors, and incorporates new entities that are defined by both histology and molecular features, including glioblastoma, IDH-wildtype and glioblastoma, IDH-mutant; diffuse midline glioma, H3 K27M-mutant; RELA fusion-positive ependymoma; medulloblastoma, WNT-activated and medulloblastoma, SHH-activated; and embryonal tumour with multilayered rosettes, C19MC-altered. The 2016 edition has added newly recognized neoplasms, and has deleted some entities, variants and patterns that no longer have diagnostic and/or biological relevance. Other notable changes include the addition of brain invasion as a criterion for atypical meningioma and the introduction of a soft tissue-type grading system for the now combined entity of solitary fibrous tumor / hemangiopericytoma-a departure from the manner by which other CNS tumors are graded. Overall, it is hoped that the 2016 CNS WHO will facilitate clinical, experimental and epidemiological studies that will lead to improvements in the lives of patients with brain tumors.
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            Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial.

            Roger Stupp, Monika E Hegi, Warren P Mason … (2009)
            In 2004, a randomised phase III trial by the European Organisation for Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trials Group (NCIC) reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and adjuvant temozolomide and radiotherapy. We report the final results with a median follow-up of more than 5 years. Adult patients with newly diagnosed glioblastoma were randomly assigned to receive either standard radiotherapy or identical radiotherapy with concomitant temozolomide followed by up to six cycles of adjuvant temozolomide. The methylation status of the methyl-guanine methyl transferase gene, MGMT, was determined retrospectively from the tumour tissue of 206 patients. The primary endpoint was overall survival. Analyses were by intention to treat. This trial is registered with Clinicaltrials.gov, number NCT00006353. Between Aug 17, 2000, and March 22, 2002, 573 patients were assigned to treatment. 278 (97%) of 286 patients in the radiotherapy alone group and 254 (89%) of 287 in the combined-treatment group died during 5 years of follow-up. Overall survival was 27.2% (95% CI 22.2-32.5) at 2 years, 16.0% (12.0-20.6) at 3 years, 12.1% (8.5-16.4) at 4 years, and 9.8% (6.4-14.0) at 5 years with temozolomide, versus 10.9% (7.6-14.8), 4.4% (2.4-7.2), 3.0% (1.4-5.7), and 1.9% (0.6-4.4) with radiotherapy alone (hazard ratio 0.6, 95% CI 0.5-0.7; p<0.0001). A benefit of combined therapy was recorded in all clinical prognostic subgroups, including patients aged 60-70 years. Methylation of the MGMT promoter was the strongest predictor for outcome and benefit from temozolomide chemotherapy. Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up. A few patients in favourable prognostic categories survive longer than 5 years. MGMT methylation status identifies patients most likely to benefit from the addition of temozolomide. EORTC, NCIC, Nélia and Amadeo Barletta Foundation, Schering-Plough.
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              Doxil®--the first FDA-approved nano-drug: lessons learned.

              Yechezkel Barenholz (2012)
              Doxil®, the first FDA-approved nano-drug (1995), is based on three unrelated principles: (i) prolonged drug circulation time and avoidance of the RES due to the use of PEGylated nano-liposomes; (ii) high and stable remote loading of doxorubicin driven by a transmembrane ammonium sulfate gradient, which also allows for drug release at the tumor; and (iii) having the liposome lipid bilayer in a "liquid ordered" phase composed of the high-T(m) (53 °C) phosphatidylcholine, and cholesterol. Due to the EPR effect, Doxil is "passively targeted" to tumors and its doxorubicin is released and becomes available to tumor cells by as yet unknown means. This review summarizes historical and scientific perspectives of Doxil development and lessons learned from its development and 20 years of its use. It demonstrates the obligatory need for applying an understanding of the cross talk between physicochemical, nano-technological, and biological principles. However, in spite of the large reward, ~2 years after Doxil-related patents expired, there is still no FDA-approved generic "Doxil" available. Copyright © 2012 Elsevier B.V. All rights reserved.
              Article 0 comments Cited 731 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): EXCLI J
                Journal ID (iso-abbrev): EXCLI J
                Journal ID (publisher-id): EXCLI J
                Title: EXCLI Journal
                Publisher: Leibniz Research Centre for Working Environment and Human Factors
                ISSN (Electronic): 1611-2156
                Publication date (Electronic): 15 November 2021
                Publication date Collection: 2021
                Volume: 20
                Pages: 1544-1570
                Affiliations
                [1 ]iMED.ULisboa, Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
                [2 ]Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
                [3 ]IBEB, Biophysics and Biomedical Engineering, Faculty of Sciences, Universidade de Lisboa, Campo Grande, 1749-016, Lisboa, Portugal
                Author notes
                *To whom correspondence should be addressed: Catarina Pinto Reis, iMED.ULisboa, Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal, E-mail: catarinareis@ 123456ff.ulisboa.pt
                Author information
                http://orcid.org/0000-0002-1046-4031
                Article
                Publisher ID: 2021-4393 Publisher ID: Doc1544
                DOI: 10.17179/excli2021-4393
                PMC ID: 8678060
                PubMed ID: 34924904
                SO-VID: d4d431d8-813a-45a7-b261-769ba3898a62
                Copyright © Copyright © 2021 Amaral et al.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence ( http://creativecommons.org/licenses/by/4.0/) You are free to copy, distribute and transmit the work, provided the original author and source are credited.

                History
                Date received : 07 October 2021
                Date accepted : 05 November 2021
                Categories
                Subject: Review Article

                Keywords: glioblastoma multiforme,nanosystems,superparamagnetic nanoparticles,polymeric nanoparticles,liposomes,gold nanoparticles
                Data availability:
                Keywords: glioblastoma multiforme, nanosystems, superparamagnetic nanoparticles, polymeric nanoparticles, liposomes, gold nanoparticles

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