Antitumor Activity of Enzastaurin (LY317615.HCl) Against Human Cancer Cell Lines and Freshly Explanted Tumors Investigated in In-vitro [corrected] Soft-agar Cloning Experiments

Overview

Journal Invest New Drugs

Publisher Springer

Specialty Oncology

Date 2007 Mar 10

PMID 17347872

Citations 13

Authors

Axel-Rainer Hanauske

Olaf Oberschmidt

Hartmut Hanauske-Abel

Michael M Lahn

Ulrike Eismann

Affiliations

Soon will be listed here.

Abstract

Enzastaurin (LY317615.HCl) is an antiproliferative agent targeted specifically against PKC-beta. 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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