Abstract:
:The phosphoinositide 3-kinase (PI3K) signaling pathway is one of the most altered in cancer, leading to a range of cellular responses including enhanced proliferation, survival, and metabolism, and is thus an attractive target for anticancer drug development. Stimulation of the PI3K pathway can be initiated by alterations at different levels of the signaling cascade including growth factor receptor activation, as well as mutations in PIK3CA, PTEN, and AKT genes frequently found in a broad range of cancers. Given its role in glucose metabolism, we investigated the utility of [(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG PET) as a pharmacodynamic biomarker of PI3K pathway-induced glucose metabolism. PTEN deletion in human colon carcinoma cells led to constitutive AKT activation but did not confer a phenotype of increased cell proliferation or glucose metabolism advantage in vivo relative to isogenic tumors derived from cells with a wild-type allele. This was not due to the activation context, that is, phosphatase activity, per se because PIK3CA activation in xenografts derived from the same lineage failed to increase glucose metabolism. Acute inhibition of PI3K activity by LY294002, and hence decreased activated AKT expression, led to a significant reduction in tumor [(18)F]FDG uptake that could be explained at least in part by decreased membrane glucose transporter 1 expression. The pharmacodynamic effect was again independent of PTEN status. In conclusion, [(18)F]FDG PET is a promising pharmacodynamic biomarker of PI3K pathway inhibition; however, its utility to detect glucose metabolism is not directly linked to the magnitude of activated AKT protein expression.
journal_name
Transl Oncoljournal_title
Translational oncologyauthors
Nguyen QD,Perumal M,Waldman TA,Aboagye EOdoi
10.1593/tlo.11118subject
Has Abstractpub_date
2011-08-01 00:00:00pages
241-8issue
4issn
1936-5233journal_volume
4pub_type
杂志文章abstract::The presence of circulating tumor cells (CTCs) in the blood of cancer patients may guide the use of therapy. We investigated how to evaluate a reduction in the number of CTCs after administration of therapy. CTCs were enumerated with the CellSearch system in 111 metastatic breast and 185 metastatic prostate cancer pat...
journal_title:Translational oncology
pub_type: 杂志文章
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journal_title:Translational oncology
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journal_title:Translational oncology
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pub_type: 杂志文章
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journal_title:Translational oncology
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journal_title:Translational oncology
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journal_title:Translational oncology
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journal_title:Translational oncology
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journal_title:Translational oncology
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journal_title:Translational oncology
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journal_title:Translational oncology
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journal_title:Translational oncology
pub_type: 杂志文章
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journal_title:Translational oncology
pub_type: 杂志文章
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更新日期:2020-10-01 00:00:00
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journal_title:Translational oncology
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.08151
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journal_title:Translational oncology
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journal_title:Translational oncology
pub_type: 杂志文章
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journal_title:Translational oncology
pub_type: 杂志文章
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更新日期:2018-02-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
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更新日期:2021-01-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
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更新日期:2009-12-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
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更新日期:2014-05-12 00:00:00
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journal_title:Translational oncology
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journal_title:Translational oncology
pub_type: 杂志文章
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更新日期:2018-08-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章,评审
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更新日期:2020-09-01 00:00:00