ALBERT

Description:    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. Content Type Journal Article Category PRECLINICAL STUDIES Pages 1-13 DOI 10.1007/s10637-011-9782-6 Authors Hyun-Jin Nam, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea Hwang-Phill Kim, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea Young-Kwang Yoon, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea Sang-Hyun Song, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea Ah-Rum Min, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea Sae-Won Han, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea Seock-Ah Im, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea Tae-You Kim, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea Do-Youn Oh, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea Yung-Jue Bang, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea Journal Investigational New Drugs Online ISSN 1573-0646 Print ISSN 0167-6997