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CIGB-300: A Promising Anti-Casein Kinase 2 (CK2) Peptide for Cancer Targeted Therapy

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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

Over the past few years, the development of CK2 inhibitors using small molecules has emerged as a paradigmatic approach for blocking the enzymatic activity. However, despite successful experimental validation, so far only one of such chemical compounds has entered into clinical trials. Using a different rationale to inhibit CK2, we have developed CIGB-300 as a novel hypothesis-driven peptide targeting the CK2 phosphoacceptor domain instead of the ATP-binding site. Data from in vitro studies have revealed that at least in human cell lines from solid tumors, CIGB-300 binds mainly to and inhibits CK2-mediated phosphorylation of B23/npm. Studies of the molecular and cellular events downstream this interaction have demonstrated that CIGB-300 induces apoptosis in vitro and in vivo, modulating a wide array of proteins involved in cell proliferation, apoptosis, ribosome biogenesis, drug resistance, cell motility, and adhesion among other processes. Accordingly, CIGB-300 has shown synergistic interaction with anticancer drugs, suppressing angiogenesis and exhibiting antimetastatic properties. The pharmacology of this peptide-based drug has already been investigated in cancer patients. Different Phase 1 clinical trials have shown CIGB-300 to be safe and well tolerated and have studied its pharmacokinetics after either local or systemic administration. Remarkably, during a dose-finding Phase 2 trial in women with cervical cancer, cohorts receiving CIGB-300 and chemoradiotherapy concomitantly had a higher frequency of complete response than those receiving chemoradiotherapy alone. Taken together, the data presented here summarize all relevant preclinical and clinical findings that make CIGB-300 a promising peptide-based drug for the treatment of cancer patients.

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Acknowledgements

We thank to C.I.G.B. and Biorec for supporting all of the work compiled in this review article. We also thank Alejandro Martin for reviewing the manuscript.

Author information

Authors and Affiliations

  1. Molecular Oncology Laboratory, Biomedical Research Area, Center for Genetic Engineering and Biotechnology, Havana, 10600, Cuba

    Silvio E. Perea, Yasser Perera & Vilcy Reyes

  2. Clinical Research Area, Center for Genetic Engineering and Biotechnology, Havana, 10600, Cuba

    Idania Baladrón, Lidia González, Idrián García, Yanelda García & Carmen Valenzuela

  3. Proteomic Department, Biomedical Research Area, Center for Genetic Engineering and Biotechnology, Havana, 10600, Cuba

    Arielis Rodríguez

  4. Molecular Oncology Laboratory, National University of Quilmes, Buenos Aires, Argentina

    Fernando Benavent, Hernán G. Fariña & Daniel F. Alonso

  5. ELEA laboratories, Buenos Aires, Argentina

    Roberto Gómez

Authors
  1. Silvio E. Perea
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  2. Yasser Perera
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  3. Idania Baladrón
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  4. Lidia González
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  13. Carmen Valenzuela
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Corresponding author

Correspondence to Silvio E. Perea .

Editor information

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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Perea, S.E. et al. (2015). CIGB-300: A Promising Anti-Casein Kinase 2 (CK2) Peptide for Cancer Targeted Therapy. 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_16

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