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A conditionally replicative, Wnt/β-catenin pathway-based adenovirus therapy for anaplastic thyroid cancer

Cancer Gene Therapy volume 14, pages 399–408 (2007)Cite this article

Abstract

Thyroid cancer affects between 10 000 and 15 000 people per year in the US. Typically, this disease can be controlled with surgical resection and radioiodide treatment. However, resistance to these conventional therapies is observed in some patients, who develop intractable anaplastic thyroid cancer (ATC), for which no effective therapies exist. Recently, a sizable fraction of undifferentiated or poorly differentiated thyroid cancers were shown to contain mutations in β-catenin, an oncogenic protein involved in the etiology of cancers of many tissues. We developed a conditionally replicative adenovirus (named ‘HILMI’) which, by virtue of TCF response elements drives E1A and E1B expression, replicates specifically in cells with an active Wnt/β-catenin pathway. We show that several thyroid cancer cell lines, derived from undifferentiated or anaplastic tissues and possessing an active Wnt/β-catenin pathway, are susceptible to cell killing by HILMI. Furthermore, viral replication in ATC cells as xenograft tumors in nude mice was observed, and prolonged survival of mice with ATC tumors was observed following administration of the HILMI therapeutic vector. The results warrant further development of this therapeutic approach for ATC patients.

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Acknowledgements

We acknowledge Sue Childress, Mark Braun, and Yanping Zhang for their technical support with microscopy studies. The authors gratefully acknowledge the following agencies for supporting this work: Thyroid Research and Advisory Council (TRAC)/Abbott Laboratories (Grant SYN-1201–07) and National Cancer Institute grant R01 CA-85289. This work is dedicated to Hilmi Abbosh who passed away during the preparation of this manuscript due to anaplastic thyroid cancer.

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Authors and Affiliations

  1. Medical Sciences and Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Bloomington, IN, USA

    P H Abbosh & K P Nephew

  2. Department of Urology, Indiana School of Medicine, Indianapolis, IN, USA

    X Li, T A Gardner & C Kao

  3. Department of Microbiology and Immunology, Indiana School of Medicine, Indianapolis, IN, USA

    X Li, T A Gardner & C Kao

  4. Division of Biostatistics, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    L Li

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  1. P H Abbosh
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Correspondence to K P Nephew.

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Abbosh, P., Li, X., Li, L. et al. A conditionally replicative, Wnt/β-catenin pathway-based adenovirus therapy for anaplastic thyroid cancer. Cancer Gene Ther 14, 399–408 (2007). https://doi.org/10.1038/sj.cgt.7701024

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