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PI3Kα Inhibitors That Inhibit Metastasis

Previous genetic analyses have suggested that mutations of the genes encoding PI3Kα facilitate invasion and metastasis but have less effect on primary tumor growth. These findings have major implications for therapeutics but have not been factored into pre-clinical drug development designs. Here we...

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Autores principales: Schmidt-Kittler, Oleg, Zhu, Jiuxiang, Yang, Jian, Liu, Guosheng, Hendricks, William, Lengauer, Christoph, Gabelli, Sandra B., Kinzler, Kenneth W., Vogelstein, Bert, Huso, David L., Zhou, Shibin
Formato: Texto
Lenguaje:English
Publicado: Impact Journals LLC 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3004370/
https://www.ncbi.nlm.nih.gov/pubmed/21179398
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author Schmidt-Kittler, Oleg
Zhu, Jiuxiang
Yang, Jian
Liu, Guosheng
Hendricks, William
Lengauer, Christoph
Gabelli, Sandra B.
Kinzler, Kenneth W.
Vogelstein, Bert
Huso, David L.
Zhou, Shibin
author_facet Schmidt-Kittler, Oleg
Zhu, Jiuxiang
Yang, Jian
Liu, Guosheng
Hendricks, William
Lengauer, Christoph
Gabelli, Sandra B.
Kinzler, Kenneth W.
Vogelstein, Bert
Huso, David L.
Zhou, Shibin
author_sort Schmidt-Kittler, Oleg
collection PubMed
description Previous genetic analyses have suggested that mutations of the genes encoding PI3Kα facilitate invasion and metastasis but have less effect on primary tumor growth. These findings have major implications for therapeutics but have not been factored into pre-clinical drug development designs. Here we show that the inhibition of PI3Kα by newly designed small molecule inhibitors prevented metastasis formation in mice but had much less effect on the growth of subcutaneous xenografts or primary intra-abdominal tumors. These data support the idea that PI3Kα plays an important role in the metastatic process and suggest a more informed strategy for selecting drugs worthy of further development for clinical application.
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spelling pubmed-30043702010-12-20 PI3Kα Inhibitors That Inhibit Metastasis Schmidt-Kittler, Oleg Zhu, Jiuxiang Yang, Jian Liu, Guosheng Hendricks, William Lengauer, Christoph Gabelli, Sandra B. Kinzler, Kenneth W. Vogelstein, Bert Huso, David L. Zhou, Shibin Oncotarget Research Papers Previous genetic analyses have suggested that mutations of the genes encoding PI3Kα facilitate invasion and metastasis but have less effect on primary tumor growth. These findings have major implications for therapeutics but have not been factored into pre-clinical drug development designs. Here we show that the inhibition of PI3Kα by newly designed small molecule inhibitors prevented metastasis formation in mice but had much less effect on the growth of subcutaneous xenografts or primary intra-abdominal tumors. These data support the idea that PI3Kα plays an important role in the metastatic process and suggest a more informed strategy for selecting drugs worthy of further development for clinical application. Impact Journals LLC 2010-09-11 /pmc/articles/PMC3004370/ /pubmed/21179398 Text en Copyright: © 2010 Schmidt-Kittler 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
spellingShingle Research Papers
Schmidt-Kittler, Oleg
Zhu, Jiuxiang
Yang, Jian
Liu, Guosheng
Hendricks, William
Lengauer, Christoph
Gabelli, Sandra B.
Kinzler, Kenneth W.
Vogelstein, Bert
Huso, David L.
Zhou, Shibin
PI3Kα Inhibitors That Inhibit Metastasis
title PI3Kα Inhibitors That Inhibit Metastasis
title_full PI3Kα Inhibitors That Inhibit Metastasis
title_fullStr PI3Kα Inhibitors That Inhibit Metastasis
title_full_unstemmed PI3Kα Inhibitors That Inhibit Metastasis
title_short PI3Kα Inhibitors That Inhibit Metastasis
title_sort pi3kα inhibitors that inhibit metastasis
topic Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3004370/
https://www.ncbi.nlm.nih.gov/pubmed/21179398
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