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Investigational New Drugs

, Volume 25, Issue 3, pp 205–210 | Cite as

Antitumor activity of enzastaurin (LY317615.HCl) against human cancer cell lines and freshly explanted tumors investigated in vitro soft-agar cloning experiments

  • Axel-Rainer Hanauske
  • Olaf OberschmidtEmail author
  • Hartmut Hanauske-Abel
  • Michael M. Lahn
  • Ulrike Eismann
PRECLINICAL STUDIES

Summary

Enzastaurin (LY317615.HCl) is an antiproliferative agent targeted specifically against PKC-β. We have investigated the antitumoral effects of Enzastaurin against human cancer cell lines and freshly explanted human tumor tissue. Ten human cancer cell lines (NSCLC, colon, and thyroid) and human tumor specimens from 72 patients were used for in vitro studies in a cloning assay (HTCA). Cell lines and primary tumor cells were exposed to Enzastaurin for either 1 h or 7 days, or for 1 h or 21 days. At clinically achievable concentrations of Enzastaurin, inhibition of cell growth was observed for lung, colorectal, and thyroid cancer cell lines in a concentration dependent manner. Patient specimens exposed 1 h or 21 days to 1,400 nM Enzastaurin demonstrated inhibition rates of 24 and 32%, respectively. Marked inhibitory effects were observed in breast, thyroid, head/neck, non-small cell lung cancer, pancreatic cancer, and melanoma. In addition to its established antiangiogenic effects, Enzastaurin has direct antitumor activity against established human cancer cell lines and primary tumor specimens. This warrants further clinical development in tumors which have been identified to be potentially sensitive to Enzastaurin.

Keywords

Enzastaurin Human tumor cloning system 

Notes

Acknowledgments

We are thankful to Eli Lilly & Company, Indianapolis, IN, USA, for support of this work.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Axel-Rainer Hanauske
    • 1
  • Olaf Oberschmidt
    • 1
    Email author
  • Hartmut Hanauske-Abel
    • 2
  • Michael M. Lahn
    • 3
  • Ulrike Eismann
    • 1
  1. 1.Asklepios Klinik St. GeorgHamburgGermany
  2. 2.UMDNJ-New Jersey Medical SchoolNewarkUSA
  3. 3.Eli Lilly & CompanyIndianapolisUSA

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