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Investigational New Drugs

, Volume 30, Issue 6, pp 2148–2160 | Cite as

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

  • Hyun-Jin Nam
  • Hwang-Phill Kim
  • Young-Kwang Yoon
  • Sang-Hyun Song
  • Ah-Rum Min
  • Sae-Won Han
  • Seock-Ah Im
  • Tae-You Kim
  • Do-Youn OhEmail author
  • Yung-Jue Bang
PRECLINICAL STUDIES

Summary

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.

Keyword

PF00299804 Irreversible pan-HER inhibitor Gemcitabine Biliary tract cancer cell lines 

Notes

Acknowledgements

This study was partially supported by a grant from the Seoul National University Hospital (grant No: 03-2009-032-0), and in part by the Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0093820).

Disclosure Statement

Yung-Jue Bang: Commercial research grant and consultant/advisory board from Pfizer Inc. Seock-Ah Im: Commercial research grant from Pfizer Inc. The other authors disclosed no potential conflicts of interest.

Supplementary material

10637_2011_9782_MOESM1_ESM.pdf (26 kb)
Supplementary Table 1 (PDF 26 kb)
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Supplementary Table 2 (PDF 26 kb)
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Supplementary Fig. 1 (PDF 34 kb)
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Supplementary Fig. 2 (PDF 58 kb)
10637_2011_9782_MOESM5_ESM.pdf (38 kb)
Supplementary Fig. 3 (PDF 37 kb)
10637_2011_9782_MOESM6_ESM.ppt (464 kb)
ESM 1 (PPT 463 kb)

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Hyun-Jin Nam
    • 1
  • Hwang-Phill Kim
    • 1
  • Young-Kwang Yoon
    • 1
  • Sang-Hyun Song
    • 1
  • Ah-Rum Min
    • 1
  • Sae-Won Han
    • 1
    • 2
  • Seock-Ah Im
    • 1
    • 2
  • Tae-You Kim
    • 1
    • 2
  • Do-Youn Oh
    • 1
    • 2
    Email author
  • Yung-Jue Bang
    • 1
    • 2
  1. 1.Cancer Research InstituteSeoul National University College of MedicineSeoulSouth Korea
  2. 2.Department of Internal Medicine, Seoul National University HospitalSeoul National University College of MedicineSeoulRepublic of Korea

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