Cargando…

Deficiency in the Treatment Description of mTOR Inhibitor Resistance in Medulloblastoma, a Systematic Review

Medulloblastoma is a common fatal pediatric brain tumor. More treatment options are required to prolong survival and decrease disability. mTOR proteins play an essential role in the disease pathogenesis, and are an essential target for therapy. Three generations of mTOR inhibitors have been develope...

Descripción completa

Detalles Bibliográficos
Autores principales: Alammar, Hajar, Nassani, Rayan, Alshehri, Mana M., Aljohani, Alaa A., Alrfaei, Bahauddeen M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8745694/
https://www.ncbi.nlm.nih.gov/pubmed/35008889
http://dx.doi.org/10.3390/ijms23010464
_version_ 1784630407274168320
author Alammar, Hajar
Nassani, Rayan
Alshehri, Mana M.
Aljohani, Alaa A.
Alrfaei, Bahauddeen M.
author_facet Alammar, Hajar
Nassani, Rayan
Alshehri, Mana M.
Aljohani, Alaa A.
Alrfaei, Bahauddeen M.
author_sort Alammar, Hajar
collection PubMed
description Medulloblastoma is a common fatal pediatric brain tumor. More treatment options are required to prolong survival and decrease disability. mTOR proteins play an essential role in the disease pathogenesis, and are an essential target for therapy. Three generations of mTOR inhibitors have been developed and are clinically used for immunosuppression and chemotherapy for multiple cancers. Only a few mTOR inhibitors have been investigated for the treatment of medulloblastoma and other pediatric tumors. The first-generation mTOR, sirolimus, temsirolimus, and everolimus, went through phase I clinical trials. The second-generation mTOR, AZD8055 and sapanisertib, suppressed medulloblastoma cell growth; however, limited studies have investigated possible resistance pathways. No clinical trials have been found to treat medulloblastoma using third-generation mTOR inhibitors. This systematic review highlights the mechanisms of resistance of mTOR inhibitors in medulloblastoma and includes IDO1, T cells, Mnk2, and eIF4E, as they prolong malignant cell survival. The findings promote the importance of combination therapy in medulloblastoma due to its highly resistant nature.
format Online
Article
Text
id pubmed-8745694
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-87456942022-01-11 Deficiency in the Treatment Description of mTOR Inhibitor Resistance in Medulloblastoma, a Systematic Review Alammar, Hajar Nassani, Rayan Alshehri, Mana M. Aljohani, Alaa A. Alrfaei, Bahauddeen M. Int J Mol Sci Review Medulloblastoma is a common fatal pediatric brain tumor. More treatment options are required to prolong survival and decrease disability. mTOR proteins play an essential role in the disease pathogenesis, and are an essential target for therapy. Three generations of mTOR inhibitors have been developed and are clinically used for immunosuppression and chemotherapy for multiple cancers. Only a few mTOR inhibitors have been investigated for the treatment of medulloblastoma and other pediatric tumors. The first-generation mTOR, sirolimus, temsirolimus, and everolimus, went through phase I clinical trials. The second-generation mTOR, AZD8055 and sapanisertib, suppressed medulloblastoma cell growth; however, limited studies have investigated possible resistance pathways. No clinical trials have been found to treat medulloblastoma using third-generation mTOR inhibitors. This systematic review highlights the mechanisms of resistance of mTOR inhibitors in medulloblastoma and includes IDO1, T cells, Mnk2, and eIF4E, as they prolong malignant cell survival. The findings promote the importance of combination therapy in medulloblastoma due to its highly resistant nature. MDPI 2021-12-31 /pmc/articles/PMC8745694/ /pubmed/35008889 http://dx.doi.org/10.3390/ijms23010464 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Alammar, Hajar
Nassani, Rayan
Alshehri, Mana M.
Aljohani, Alaa A.
Alrfaei, Bahauddeen M.
Deficiency in the Treatment Description of mTOR Inhibitor Resistance in Medulloblastoma, a Systematic Review
title Deficiency in the Treatment Description of mTOR Inhibitor Resistance in Medulloblastoma, a Systematic Review
title_full Deficiency in the Treatment Description of mTOR Inhibitor Resistance in Medulloblastoma, a Systematic Review
title_fullStr Deficiency in the Treatment Description of mTOR Inhibitor Resistance in Medulloblastoma, a Systematic Review
title_full_unstemmed Deficiency in the Treatment Description of mTOR Inhibitor Resistance in Medulloblastoma, a Systematic Review
title_short Deficiency in the Treatment Description of mTOR Inhibitor Resistance in Medulloblastoma, a Systematic Review
title_sort deficiency in the treatment description of mtor inhibitor resistance in medulloblastoma, a systematic review
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8745694/
https://www.ncbi.nlm.nih.gov/pubmed/35008889
http://dx.doi.org/10.3390/ijms23010464
work_keys_str_mv AT alammarhajar deficiencyinthetreatmentdescriptionofmtorinhibitorresistanceinmedulloblastomaasystematicreview
AT nassanirayan deficiencyinthetreatmentdescriptionofmtorinhibitorresistanceinmedulloblastomaasystematicreview
AT alshehrimanam deficiencyinthetreatmentdescriptionofmtorinhibitorresistanceinmedulloblastomaasystematicreview
AT aljohanialaaa deficiencyinthetreatmentdescriptionofmtorinhibitorresistanceinmedulloblastomaasystematicreview
AT alrfaeibahauddeenm deficiencyinthetreatmentdescriptionofmtorinhibitorresistanceinmedulloblastomaasystematicreview