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Recent advances and limitations of mTOR inhibitors in the treatment of cancer

The PI3K-Akt-mechanistic (formerly mammalian) target of the rapamycin (mTOR) signaling pathway is important in a variety of biological activities, including cellular proliferation, survival, metabolism, autophagy, and immunity. Abnormal PI3K-Akt-mTOR signalling activation can promote transformation...

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Autores principales: Ali, Eunus S., Mitra, Kangkana, Akter, Shamima, Ramproshad, Sarker, Mondal, Banani, Khan, Ishaq N., Islam, Muhammad Torequl, Sharifi-Rad, Javad, Calina, Daniela, Cho, William C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476305/
https://www.ncbi.nlm.nih.gov/pubmed/36109789
http://dx.doi.org/10.1186/s12935-022-02706-8
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author Ali, Eunus S.
Mitra, Kangkana
Akter, Shamima
Ramproshad, Sarker
Mondal, Banani
Khan, Ishaq N.
Islam, Muhammad Torequl
Sharifi-Rad, Javad
Calina, Daniela
Cho, William C.
author_facet Ali, Eunus S.
Mitra, Kangkana
Akter, Shamima
Ramproshad, Sarker
Mondal, Banani
Khan, Ishaq N.
Islam, Muhammad Torequl
Sharifi-Rad, Javad
Calina, Daniela
Cho, William C.
author_sort Ali, Eunus S.
collection PubMed
description The PI3K-Akt-mechanistic (formerly mammalian) target of the rapamycin (mTOR) signaling pathway is important in a variety of biological activities, including cellular proliferation, survival, metabolism, autophagy, and immunity. Abnormal PI3K-Akt-mTOR signalling activation can promote transformation by creating a cellular environment conducive to it. Deregulation of such a system in terms of genetic mutations and amplification has been related to several human cancers. Consequently, mTOR has been recognized as a key target for the treatment of cancer, especially for treating cancers with elevated mTOR signaling due to genetic or metabolic disorders. In vitro and in vivo, rapamycin which is an immunosuppressant agent actively suppresses the activity of mTOR and reduces cancer cell growth. As a result, various sirolimus-derived compounds have now been established as therapies for cancer, and now these medications are being investigated in clinical studies. In this updated review, we discuss the usage of sirolimus-derived compounds and other drugs in several preclinical or clinical studies as well as explain some of the challenges involved in targeting mTOR for treating various human cancers.
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spelling pubmed-94763052022-09-16 Recent advances and limitations of mTOR inhibitors in the treatment of cancer Ali, Eunus S. Mitra, Kangkana Akter, Shamima Ramproshad, Sarker Mondal, Banani Khan, Ishaq N. Islam, Muhammad Torequl Sharifi-Rad, Javad Calina, Daniela Cho, William C. Cancer Cell Int Review The PI3K-Akt-mechanistic (formerly mammalian) target of the rapamycin (mTOR) signaling pathway is important in a variety of biological activities, including cellular proliferation, survival, metabolism, autophagy, and immunity. Abnormal PI3K-Akt-mTOR signalling activation can promote transformation by creating a cellular environment conducive to it. Deregulation of such a system in terms of genetic mutations and amplification has been related to several human cancers. Consequently, mTOR has been recognized as a key target for the treatment of cancer, especially for treating cancers with elevated mTOR signaling due to genetic or metabolic disorders. In vitro and in vivo, rapamycin which is an immunosuppressant agent actively suppresses the activity of mTOR and reduces cancer cell growth. As a result, various sirolimus-derived compounds have now been established as therapies for cancer, and now these medications are being investigated in clinical studies. In this updated review, we discuss the usage of sirolimus-derived compounds and other drugs in several preclinical or clinical studies as well as explain some of the challenges involved in targeting mTOR for treating various human cancers. BioMed Central 2022-09-15 /pmc/articles/PMC9476305/ /pubmed/36109789 http://dx.doi.org/10.1186/s12935-022-02706-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Review
Ali, Eunus S.
Mitra, Kangkana
Akter, Shamima
Ramproshad, Sarker
Mondal, Banani
Khan, Ishaq N.
Islam, Muhammad Torequl
Sharifi-Rad, Javad
Calina, Daniela
Cho, William C.
Recent advances and limitations of mTOR inhibitors in the treatment of cancer
title Recent advances and limitations of mTOR inhibitors in the treatment of cancer
title_full Recent advances and limitations of mTOR inhibitors in the treatment of cancer
title_fullStr Recent advances and limitations of mTOR inhibitors in the treatment of cancer
title_full_unstemmed Recent advances and limitations of mTOR inhibitors in the treatment of cancer
title_short Recent advances and limitations of mTOR inhibitors in the treatment of cancer
title_sort recent advances and limitations of mtor inhibitors in the treatment of cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476305/
https://www.ncbi.nlm.nih.gov/pubmed/36109789
http://dx.doi.org/10.1186/s12935-022-02706-8
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