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In vitro evaluation of clinical activity and toxicity of anticancer drugs using tumor cells from patients and cells representing normal tissues

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Abstract

Purpose

The aim of this study was to evaluate a phenotypic cell panel with tumor cells from various patients and normal cells for preclinical profiles of antitumor efficacy and toxicity of anticancer drugs.

Methods

The antitumor activity of fourteen anticancer drugs was tested in over one hundred tumor samples from patients with solid or hematological malignancies. Drug activity against four normal cell types was used for the assessment of normal tissue toxicity. In vitro activity of the drugs was compared with indications approved by the Food and Drug Administration and established adverse event profiles.

Results

In general, in vitro drug activity in tumor cells from patients reflected known clinical activity of the drugs investigated. For example, the clinical activity of imatinib in chronic myeloid leukemia was clearly detected in the tumor panel. Further, and in accordance with clinical use, cisplatin and bortezomib showed high activity in ovarian cancer and myeloma samples, respectively. The normal cell models roughly reflected known clinical toxicity profiles and were able to detect differences in therapeutic index, e.g., between targeted drugs and classical cytotoxic agents. For example, the high tolerability of imatinib and the well-known renal toxicity of cisplatin were demonstrated.

Conclusions

In preclinical drug development, primary tumor cells from patients can be used for the prediction of cancer diagnosis–specific activity and may aid in the selection of diagnoses for clinical trials. By using tumor and toxicity panels together, information about therapeutic index may be derived, which may be useful when choosing among drug candidates with similar tumor effects.

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Acknowledgments

The skillful technical assistance of Anna-Karin Lannergård, Christina Leek, Lena Lenhammar, David Munro and Linda Rickardson is gratefully acknowledged.

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Authors and Affiliations

  1. Division of Clinical Pharmacology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden

    Caroline Haglund, Peter Nygren, Joachim Gullbo, Malin Wickström, Rolf Larsson & Elin Lindhagen

  2. Division of Haematology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden

    Anna Åleskog & Martin Höglund

  3. Division of Oncology, Department of Oncology and Radiation Sciences , Uppsala University, Uppsala, Sweden

    Peter Nygren

Authors
  1. Caroline Haglund
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  2. Anna Åleskog
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  3. Peter Nygren
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  4. Joachim Gullbo
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  5. Martin Höglund
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  6. Malin Wickström
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  7. Rolf Larsson
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  8. Elin Lindhagen
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Corresponding author

Correspondence to Caroline Haglund.

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Haglund, C., Åleskog, A., Nygren, P. et al. In vitro evaluation of clinical activity and toxicity of anticancer drugs using tumor cells from patients and cells representing normal tissues. Cancer Chemother Pharmacol 69, 697–707 (2012). https://doi.org/10.1007/s00280-011-1746-1

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  • DOI: https://doi.org/10.1007/s00280-011-1746-1

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