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

Autor: Eliot T McKinley, Ping Zhao, Robert J Coffey, M Kay Washington, H Charles Manning
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: PLoS ONE, Vol 9, Iss 9, p e108193 (2014)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0108193
Popis: 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.
Databáze: Directory of Open Access Journals