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The irreversible pan-HER inhibitor PF00299804 alone or combined with gemcitabine has an antitumor effect in biliary tract cancer cell lines

Cited 12 time in Web of Science Cited 12 time in Scopus
Authors
Nam, Hyun-Jin; Kim, Hwang-Phill; Yoon, Young-Kwang; Song, Sang-Hyun; Min, Ah-Rum; Han, Sae-Won; Im, Seock-Ah; Kim, Tae-You; Oh, Do-Youn; Bang, Yung-Jue
Issue Date
2012-12
Citation
Investigational New Drugs, Vol.30 No.6, pp.2148-2160
Keywords
PF00299804Irreversible pan-HER inhibitorGemcitabineBiliary tract cancer cell lines
Abstract
Biliary tract cancer (BTC) is associated with poor survival and unresponsiveness to chemotherapy. Targeted therapies for BTC have been studied, and HER family members are promising therapeutic targets in BTC. In this study, we evaluated the efficacy of PF00299804, an irreversible pan-HER inhibitor, in eight BTC cell lines alone or combined with gemcitabine. PF00299804 potently inhibited the growth of two cell lines (SNU308 and SNU478) out of the eight BTC cell lines as a single agent. PF00299804 blocked HER family and downstream signaling pathways, inducing G1 arrest or apoptosis. Moreover, PF00299804 exerted synergistic effects with gemcitabine in seven of the eight BTC cell lines, possibly through the regulation of the genes involved in the response to gemcitabine, such as TS (thymidylate synthase), RRM1 (ribonucleotide reductase), and MAGEH1, which is negatively correlated with gemcitabine sensitivity. Our results support the need for further study of PF00299804 alone or combined with gemcitabine for the treatment of BTC.
ISSN
0167-6997
URI
https://hdl.handle.net/10371/173139
DOI
https://doi.org/10.1007/s10637-011-9782-6
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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