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Targeting CK2 for Cancer Therapy Using a Nanomedicine Approach

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Protein Kinase CK2 Cellular Function in Normal and Disease States

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 12))

Abstract

CK2 is a signal-responsive serine/threonine protein kinase which promotes cell proliferation, suppresses apoptosis, and demonstrates increased expression in numerous cancers. Here, we present information on investigations into CK2-focused cancer therapy in general and discuss in detail a nanomedicine approach to targeting CK2 in a cancer cell-specific manner. Specifically, we summarize data on biodistribution and therapeutic efficacy of a tenfibgen (TBG) nanoencapsulation technology for the delivery of anti-CK2 cargos to malignant cells. The TBG nanocapsule cargos discussed include siRNA (siCK2), single-stranded DNA/RNA chimeric oligonucleotides (RNAi-CK2), and a small-molecule CK2 inhibitor (DMAT). Systemic administration of TBG-RNAi-CK2 resulted in xenograft tumor reduction using low doses with concomitant reduction in CK2 protein expression. Systemic TBG-DMAT treatment decreased xenograft tumor proliferation. No toxicity or early inflammation response was observed after using any of the TBG encapsulated anti-CK2 cargos. The utility of this therapy approach for targeting metastatic cancer sites and on overall survival is also discussed. Protected and malignant cell-specific delivery of a therapeutic is a promising target-specific and versatile approach for cancer therapy, and both the TBG encapsulation technology and the anti-CK2 oligonucleotide approach demonstrate substantial potential for the treatment of malignancy.

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Authors and Affiliations

  1. Department of Laboratory Medicine and Pathology, University of Minnesota Medical School and Minneapolis VA Health Care System, Minneapolis, MN, USA

    Khalil Ahmed

  2. GeneSegues, Inc., Chaska, MN, 55318, USA

    Gretchen Unger

  3. Cellular and Molecular Biochemistry Research Laboratory (151), Minneapolis Veterans Affairs Health Care System, One Veterans Drive, Minneapolis, MN, 55417, USA

    Betsy T. Kren & Janeen H. Trembley

  4. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, 55455, USA

    Betsy T. Kren & Janeen H. Trembley

  5. Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, USA

    Betsy T. Kren & Janeen H. Trembley

  6. Cellular and Molecular Biochemistry Research Laboratory (151), Veterans Affairs Medical Center, Minneapolis, MN, USA

    Betsy T. Kren & Janeen H. Trembley

Authors
  1. Khalil Ahmed
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  2. Gretchen Unger
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  3. Betsy T. Kren
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  4. Janeen H. Trembley
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Correspondence to Janeen H. Trembley .

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Editors and Affiliations

  1. Department of Laboratory Medicine and Pathology, University of Minnesota Medical School and Minneapolis VA Health Care System, Minneapolis, Minnesota, USA

    Khalil Ahmed

  2. Dept of Biochemistry & Molecular Biology, University of Southern Denmark, Odense, Denmark

    Olaf-Georg Issinger

  3. Department of Molecular Biology, The John Paul II Catholic U. of Lublin Institute of Biotechnology, Lublin, Poland

    Ryszard Szyszka

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Ahmed, K., Unger, G., Kren, B.T., Trembley, J.H. (2015). Targeting CK2 for Cancer Therapy Using a Nanomedicine Approach. In: Ahmed, K., Issinger, OG., Szyszka, R. (eds) Protein Kinase CK2 Cellular Function in Normal and Disease States. Advances in Biochemistry in Health and Disease, vol 12. Springer, Cham. https://doi.org/10.1007/978-3-319-14544-0_17

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