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JAK2-STAT5 signaling: A novel mechanism of resistance to targeted PI3K/mTOR inhibition

A recent article published by Britschgi et al. in Cancer Cell, “JAK2/STAT5 Inhibition Circumvents Resistance to PI3K/mTOR Blockade: A Rationale for Cotargeting These Pathways in Metastatic Breast Cancer,” describes a positive feedback loop of JAK2/STAT5 activation that drives resistance to PI3K/mTOR...

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Detalles Bibliográficos
Autores principales: Yeh, Jennifer E, Toniolo, Patricia A, Frank, David A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Landes Bioscience 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891630/
https://www.ncbi.nlm.nih.gov/pubmed/24470973
http://dx.doi.org/10.4161/jkst.24635
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author Yeh, Jennifer E
Toniolo, Patricia A
Frank, David A
author_facet Yeh, Jennifer E
Toniolo, Patricia A
Frank, David A
author_sort Yeh, Jennifer E
collection PubMed
description A recent article published by Britschgi et al. in Cancer Cell, “JAK2/STAT5 Inhibition Circumvents Resistance to PI3K/mTOR Blockade: A Rationale for Cotargeting These Pathways in Metastatic Breast Cancer,” describes a positive feedback loop of JAK2/STAT5 activation that drives resistance to PI3K/mTOR inhibition in breast cancer. The authors found that genetic or pharmacological inhibition of JAK2 circumvents resistance to PI3K/mTOR inhibition and go on to show the efficacy of combined PI3K/mTOR and JAK2 inhibition on reducing cancer cell number, tumor growth, and metastasis as well as increasing in vivo survival. These results provide strong support for combination therapy with JAK2/STAT5 and PI3K/mTOR inhibitors in breast cancer. Here we discuss how the article by Britschgi et al. proposes a novel mechanism to explain how breast cancer cells overcome inhibition of a key signaling pathway driving cell proliferation. We also discuss the interplay between activation of the transcription factors STAT5 and STAT3 in breast cancer.
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spelling pubmed-38916302014-01-27 JAK2-STAT5 signaling: A novel mechanism of resistance to targeted PI3K/mTOR inhibition Yeh, Jennifer E Toniolo, Patricia A Frank, David A JAKSTAT Commentary A recent article published by Britschgi et al. in Cancer Cell, “JAK2/STAT5 Inhibition Circumvents Resistance to PI3K/mTOR Blockade: A Rationale for Cotargeting These Pathways in Metastatic Breast Cancer,” describes a positive feedback loop of JAK2/STAT5 activation that drives resistance to PI3K/mTOR inhibition in breast cancer. The authors found that genetic or pharmacological inhibition of JAK2 circumvents resistance to PI3K/mTOR inhibition and go on to show the efficacy of combined PI3K/mTOR and JAK2 inhibition on reducing cancer cell number, tumor growth, and metastasis as well as increasing in vivo survival. These results provide strong support for combination therapy with JAK2/STAT5 and PI3K/mTOR inhibitors in breast cancer. Here we discuss how the article by Britschgi et al. proposes a novel mechanism to explain how breast cancer cells overcome inhibition of a key signaling pathway driving cell proliferation. We also discuss the interplay between activation of the transcription factors STAT5 and STAT3 in breast cancer. Landes Bioscience 2013-10-01 2013-04-15 /pmc/articles/PMC3891630/ /pubmed/24470973 http://dx.doi.org/10.4161/jkst.24635 Text en Copyright © 2013 Landes Bioscience http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Commentary
Yeh, Jennifer E
Toniolo, Patricia A
Frank, David A
JAK2-STAT5 signaling: A novel mechanism of resistance to targeted PI3K/mTOR inhibition
title JAK2-STAT5 signaling: A novel mechanism of resistance to targeted PI3K/mTOR inhibition
title_full JAK2-STAT5 signaling: A novel mechanism of resistance to targeted PI3K/mTOR inhibition
title_fullStr JAK2-STAT5 signaling: A novel mechanism of resistance to targeted PI3K/mTOR inhibition
title_full_unstemmed JAK2-STAT5 signaling: A novel mechanism of resistance to targeted PI3K/mTOR inhibition
title_short JAK2-STAT5 signaling: A novel mechanism of resistance to targeted PI3K/mTOR inhibition
title_sort jak2-stat5 signaling: a novel mechanism of resistance to targeted pi3k/mtor inhibition
topic Commentary
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891630/
https://www.ncbi.nlm.nih.gov/pubmed/24470973
http://dx.doi.org/10.4161/jkst.24635
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