Role of dual PI3/Akt and mTOR inhibition in Waldenstrom's Macroglobulinemia

Role of dual PI3/Akt and mTOR inhibition in Waldenstrom's Macroglobulinemia

Tumorigenesis occurs due to synergistic interactions from a complex of signal transduction processes, including multiple onco-proteins and tumor suppressors such as Ras, Myc, PI3K/Akt/mTOR, Her-2/Neu, p53 and PTEN. Specifically, the PI3K/Akt and mTOR pathways have been shown to play a pivotal role o...

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Main Authors: Sacco, Antonio, Roccaro, Aldo, Ghobrial, Irene M.
Format: Online
Language:English
Published: Impact Journals LLC 2010
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248138/
id pubmed-3248138
recordtype oai_dc
spelling pubmed-32481382012-01-18 Role of dual PI3/Akt and mTOR inhibition in Waldenstrom's Macroglobulinemia Sacco, Antonio Roccaro, Aldo Ghobrial, Irene M. Reviews Tumorigenesis occurs due to synergistic interactions from a complex of signal transduction processes, including multiple onco-proteins and tumor suppressors such as Ras, Myc, PI3K/Akt/mTOR, Her-2/Neu, p53 and PTEN. Specifically, the PI3K/Akt and mTOR pathways have been shown to play a pivotal role on the initiation and progression of malignancies, enhancing cell survival by stimulating cell proliferation, and inhibiting apoptosis. Therefore, it is critical to examine therapeutic agents that explicitly target both the PI3K/Akt and mTOR signaling cascades in diseases, such as Waldenstrom Macroglobulinemia (WM), that harbor activation of the PI3K/Akt pathway. We demonstrated that dual targeting of the PI3K and mTOR pathways by the novel inhibitor NVP-BEZ235, exhibited toxicity on WM cells by directly targeting the tumor clone and indirectly through an effect on the bone marrow milieu. These findings suggest that dual targeting of the PI3K and mTOR pathways is a better modality of targeted therapy for tumors that harbor activation of the PI3K/mTOR pathways, such as in WM. Impact Journals LLC 2010-11-17 /pmc/articles/PMC3248138/ /pubmed/21317453 Text en Copyright: © 2010 Sacco et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Sacco, Antonio
Roccaro, Aldo
Ghobrial, Irene M.
spellingShingle Sacco, Antonio
Roccaro, Aldo
Ghobrial, Irene M.
Role of dual PI3/Akt and mTOR inhibition in Waldenstrom's Macroglobulinemia
author_facet Sacco, Antonio
Roccaro, Aldo
Ghobrial, Irene M.
author_sort Sacco, Antonio
title Role of dual PI3/Akt and mTOR inhibition in Waldenstrom's Macroglobulinemia
title_short Role of dual PI3/Akt and mTOR inhibition in Waldenstrom's Macroglobulinemia
title_full Role of dual PI3/Akt and mTOR inhibition in Waldenstrom's Macroglobulinemia
title_fullStr Role of dual PI3/Akt and mTOR inhibition in Waldenstrom's Macroglobulinemia
title_full_unstemmed Role of dual PI3/Akt and mTOR inhibition in Waldenstrom's Macroglobulinemia
title_sort role of dual pi3/akt and mtor inhibition in waldenstrom's macroglobulinemia
description Tumorigenesis occurs due to synergistic interactions from a complex of signal transduction processes, including multiple onco-proteins and tumor suppressors such as Ras, Myc, PI3K/Akt/mTOR, Her-2/Neu, p53 and PTEN. Specifically, the PI3K/Akt and mTOR pathways have been shown to play a pivotal role on the initiation and progression of malignancies, enhancing cell survival by stimulating cell proliferation, and inhibiting apoptosis. Therefore, it is critical to examine therapeutic agents that explicitly target both the PI3K/Akt and mTOR signaling cascades in diseases, such as Waldenstrom Macroglobulinemia (WM), that harbor activation of the PI3K/Akt pathway. We demonstrated that dual targeting of the PI3K and mTOR pathways by the novel inhibitor NVP-BEZ235, exhibited toxicity on WM cells by directly targeting the tumor clone and indirectly through an effect on the bone marrow milieu. These findings suggest that dual targeting of the PI3K and mTOR pathways is a better modality of targeted therapy for tumors that harbor activation of the PI3K/mTOR pathways, such as in WM.
publisher Impact Journals LLC
publishDate 2010
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248138/
_version_ 1611497267355713536

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