3'-Deoxy-3'-[18F]-Fluorothymidine PET imaging reflects PI3K-mTOR-mediated pro-survival response to targeted therapy in colorectal cancer

Biomarkers that predict response to targeted therapy in oncology are an essential component of personalized medicine. In preclinical treatment response studies that featured models of wild-type KRAS or mutant BRAF colorectal cancer treated with either cetuximab or vemurafenib, respectively, we illus...

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Bibliographic Details
Published in:PloS one 2014-09, Vol.9 (9), p.e108193-e108193
Main Authors: McKinley, Eliot T, Zhao, Ping, Coffey, Robert J, Washington, M Kay, Manning, H Charles
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
Animals
Antineoplastic Agents - therapeutic use
Bioindicators
Biomarkers
Biomedical engineering
Cancer
Cancer therapies
Cancer treatment
Cell Line, Tumor
Cetuximab - therapeutic use
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - diagnostic imaging
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - metabolism
Health aspects
K-Ras protein
Kinases
MAP kinase
Medical imaging
Medical schools
Medicine
Medicine and Health Sciences
Melanoma
Mice
Mice, Nude
Monoclonal antibodies
Oncology
Phosphatidylinositol 3-Kinases - metabolism
Positron emission
Positron emission tomography
Precision medicine
Salvage
Solid tumors
Survival
Targeted cancer therapy
Therapy
Thymidine
Tomography
TOR protein
TOR Serine-Threonine Kinases - metabolism
Tumors
Vultur
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Summary:Biomarkers that predict response to targeted therapy in oncology are an essential component of personalized medicine. In preclinical treatment response studies that featured models of wild-type KRAS or mutant BRAF colorectal cancer treated with either cetuximab or vemurafenib, respectively, we illustrate that [(18)F]-FLT PET, a non-invasive molecular imaging readout of thymidine salvage, closely reflects pro-survival responses to targeted therapy that are mediated by PI3K-mTOR activity. Activation of pro-survival mechanisms forms the basis of numerous modes of resistance. Therefore, we conclude that [(18)F]-FLT PET may serve a novel and potentially critical role to predict tumors that exhibit molecular features that tend to reflect recalcitrance to MAPK-targeted therapy. Though these studies focused on colorectal cancer, we envision that the results may be applicable to other solid tumors as well.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0108193