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JAK/STAT Signaling: Molecular Targets, Therapeutic Opportunities, and Limitations of Targeted Inhibitions in Solid Malignancies

JAK/STAT signaling pathway is one of the important regulatory signaling cascades for the myriad of cellular processes initiated by various types of ligands such as growth factors, hormones, and cytokines. The physiological processes regulated by JAK/STAT signaling are immune regulation, cell prolife...

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Autores principales: Rah, Bilal, Rather, Rafiq A, Bhat, Gh Rasool, Baba, Abdul Basit, Mushtaq, Ifra, Farooq, Muzamil, Yousuf, Tahira, Dar, Sadaf B, Parveen, Sabra, Hassan, Rukhsana, Mohammad, Fozia, Qassim, Iqbal, Bhat, Abida, Ali, Shazia, Zargar, Mahrukh Hamid, Afroze, Dil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8987160/
https://www.ncbi.nlm.nih.gov/pubmed/35401182
http://dx.doi.org/10.3389/fphar.2022.821344
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author Rah, Bilal
Rather, Rafiq A
Bhat, Gh Rasool
Baba, Abdul Basit
Mushtaq, Ifra
Farooq, Muzamil
Yousuf, Tahira
Dar, Sadaf B
Parveen, Sabra
Hassan, Rukhsana
Mohammad, Fozia
Qassim, Iqbal
Bhat, Abida
Ali, Shazia
Zargar, Mahrukh Hamid
Afroze, Dil
author_facet Rah, Bilal
Rather, Rafiq A
Bhat, Gh Rasool
Baba, Abdul Basit
Mushtaq, Ifra
Farooq, Muzamil
Yousuf, Tahira
Dar, Sadaf B
Parveen, Sabra
Hassan, Rukhsana
Mohammad, Fozia
Qassim, Iqbal
Bhat, Abida
Ali, Shazia
Zargar, Mahrukh Hamid
Afroze, Dil
author_sort Rah, Bilal
collection PubMed
description JAK/STAT signaling pathway is one of the important regulatory signaling cascades for the myriad of cellular processes initiated by various types of ligands such as growth factors, hormones, and cytokines. The physiological processes regulated by JAK/STAT signaling are immune regulation, cell proliferation, cell survival, apoptosis and hematopoiesis of myeloid and non-myeloid cells. Dysregulation of JAK/STAT signaling is reported in various immunological disorders, hematological and other solid malignancies through various oncogenic activation mutations in receptors, downstream mediators, and associated transcriptional factors such as STATs. STATs typically have a dual role when explored in the context of cancer. While several members of the STAT family are involved in malignancies, however, a few members which include STAT3 and STAT5 are linked to tumor initiation and progression. Other STAT members such as STAT1 and STAT2 are pivotal for antitumor defense and maintenance of an effective and long-term immune response through evolutionarily conserved programs. The effects of JAK/STAT signaling and the persistent activation of STATs in tumor cell survival; proliferation and invasion have made the JAK/STAT pathway an ideal target for drug development and cancer therapy. Therefore, understanding the intricate JAK/STAT signaling in the pathogenesis of solid malignancies needs extensive research. A better understanding of the functionally redundant roles of JAKs and STATs may provide a rationale for improving existing cancer therapies which have deleterious effects on normal cells and to identifying novel targets for therapeutic intervention in solid malignancies.
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spelling pubmed-89871602022-04-08 JAK/STAT Signaling: Molecular Targets, Therapeutic Opportunities, and Limitations of Targeted Inhibitions in Solid Malignancies Rah, Bilal Rather, Rafiq A Bhat, Gh Rasool Baba, Abdul Basit Mushtaq, Ifra Farooq, Muzamil Yousuf, Tahira Dar, Sadaf B Parveen, Sabra Hassan, Rukhsana Mohammad, Fozia Qassim, Iqbal Bhat, Abida Ali, Shazia Zargar, Mahrukh Hamid Afroze, Dil Front Pharmacol Pharmacology JAK/STAT signaling pathway is one of the important regulatory signaling cascades for the myriad of cellular processes initiated by various types of ligands such as growth factors, hormones, and cytokines. The physiological processes regulated by JAK/STAT signaling are immune regulation, cell proliferation, cell survival, apoptosis and hematopoiesis of myeloid and non-myeloid cells. Dysregulation of JAK/STAT signaling is reported in various immunological disorders, hematological and other solid malignancies through various oncogenic activation mutations in receptors, downstream mediators, and associated transcriptional factors such as STATs. STATs typically have a dual role when explored in the context of cancer. While several members of the STAT family are involved in malignancies, however, a few members which include STAT3 and STAT5 are linked to tumor initiation and progression. Other STAT members such as STAT1 and STAT2 are pivotal for antitumor defense and maintenance of an effective and long-term immune response through evolutionarily conserved programs. The effects of JAK/STAT signaling and the persistent activation of STATs in tumor cell survival; proliferation and invasion have made the JAK/STAT pathway an ideal target for drug development and cancer therapy. Therefore, understanding the intricate JAK/STAT signaling in the pathogenesis of solid malignancies needs extensive research. A better understanding of the functionally redundant roles of JAKs and STATs may provide a rationale for improving existing cancer therapies which have deleterious effects on normal cells and to identifying novel targets for therapeutic intervention in solid malignancies. Frontiers Media S.A. 2022-03-24 /pmc/articles/PMC8987160/ /pubmed/35401182 http://dx.doi.org/10.3389/fphar.2022.821344 Text en Copyright © 2022 Rah, Rather, Bhat, Baba, Mushtaq, Farooq, Yousuf, Dar, Parveen, Hassan, Mohammad, Qassim, Bhat, Ali, Zargar and Afroze. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Rah, Bilal
Rather, Rafiq A
Bhat, Gh Rasool
Baba, Abdul Basit
Mushtaq, Ifra
Farooq, Muzamil
Yousuf, Tahira
Dar, Sadaf B
Parveen, Sabra
Hassan, Rukhsana
Mohammad, Fozia
Qassim, Iqbal
Bhat, Abida
Ali, Shazia
Zargar, Mahrukh Hamid
Afroze, Dil
JAK/STAT Signaling: Molecular Targets, Therapeutic Opportunities, and Limitations of Targeted Inhibitions in Solid Malignancies
title JAK/STAT Signaling: Molecular Targets, Therapeutic Opportunities, and Limitations of Targeted Inhibitions in Solid Malignancies
title_full JAK/STAT Signaling: Molecular Targets, Therapeutic Opportunities, and Limitations of Targeted Inhibitions in Solid Malignancies
title_fullStr JAK/STAT Signaling: Molecular Targets, Therapeutic Opportunities, and Limitations of Targeted Inhibitions in Solid Malignancies
title_full_unstemmed JAK/STAT Signaling: Molecular Targets, Therapeutic Opportunities, and Limitations of Targeted Inhibitions in Solid Malignancies
title_short JAK/STAT Signaling: Molecular Targets, Therapeutic Opportunities, and Limitations of Targeted Inhibitions in Solid Malignancies
title_sort jak/stat signaling: molecular targets, therapeutic opportunities, and limitations of targeted inhibitions in solid malignancies
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8987160/
https://www.ncbi.nlm.nih.gov/pubmed/35401182
http://dx.doi.org/10.3389/fphar.2022.821344
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