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

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An Erratum to this article was published on 18 April 2007

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.

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Acknowledgments

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

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Authors and Affiliations

  1. Asklepios Klinik St. Georg, Lohmühlenstr. 5, 20099, Hamburg, Germany

    Axel-Rainer Hanauske, Olaf Oberschmidt & Ulrike Eismann

  2. UMDNJ-New Jersey Medical School, Newark, NJ, 07103-2714, USA

    Hartmut Hanauske-Abel

  3. Eli Lilly & Company, Indianapolis, IN, 46285, USA

    Michael M. Lahn

Authors
  1. Axel-Rainer Hanauske
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  2. Olaf Oberschmidt
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  3. Hartmut Hanauske-Abel
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  4. Michael M. Lahn
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  5. Ulrike Eismann
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Corresponding author

Correspondence to Olaf Oberschmidt.

Additional information

Hanauske and Oberschmidt have contributed equally to this project.

An erratum to this article can be found at http://dx.doi.org/10.1007/s10637-007-9051-x

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Hanauske, AR., Oberschmidt, O., Hanauske-Abel, H. et al. Antitumor activity of enzastaurin (LY317615.HCl) against human cancer cell lines and freshly explanted tumors investigated in vitro soft-agar cloning experiments. Invest New Drugs 25, 205–210 (2007). https://doi.org/10.1007/s10637-007-9038-7

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  • DOI: https://doi.org/10.1007/s10637-007-9038-7

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