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Targeting CK2 for Cancer Therapy Using a Nanomedicine Approach

  • Khalil Ahmed
  • Gretchen Unger
  • Betsy T. Kren
  • Janeen H. TrembleyEmail author
Chapter
Part of the Advances in Biochemistry in Health and Disease book series (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.

Keywords

CK2 Antisense RNAi siRNA DMAT Nanocapsule Nanoparticle Nanomedicine Xenograft Prostate HNSCC Biodistribution Metastasis 

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Khalil Ahmed
    • 1
  • Gretchen Unger
    • 2
  • Betsy T. Kren
    • 3
    • 4
    • 5
    • 6
  • Janeen H. Trembley
    • 3
    • 4
    • 5
    • 6
    Email author
  1. 1.Department of Laboratory Medicine and PathologyUniversity of Minnesota Medical School and Minneapolis VA Health Care SystemMinneapolisUSA
  2. 2.GeneSegues, Inc.ChaskaUSA
  3. 3.Cellular and Molecular Biochemistry Research Laboratory (151), Minneapolis Veterans Affairs Health Care SystemMinneapolisUSA
  4. 4.Department of Laboratory Medicine and PathologyUniversity of MinnesotaMinneapolisUSA
  5. 5.Masonic Cancer Center, University of MinnesotaMinneapolisUSA
  6. 6.Cellular and Molecular Biochemistry Research Laboratory (151), Veterans Affairs Medical CenterMinneapolisUSA

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