CIGB-300, a synthetic peptide-based drug that targets the CK2 phosphoaceptor domain. Translational and clinical research

  • Silvio E. Perea
  • Idania Baladron
  • Yanelda Garcia
  • Yasser Perera
  • Adlin Lopez
  • Jorge L. Soriano
  • Noyde Batista
  • Aley Palau
  • Ignacio Hernández
  • Hernán Farina
  • Idrian Garcia
  • Lidia Gonzalez
  • Jeovanis Gil
  • Arielis Rodriguez
  • Margarita Solares
  • Agueda Santana
  • Marisol Cruz
  • Matilde Lopez
  • Carmen Valenzuela
  • Osvaldo Reyes
  • Pedro A. López-Saura
  • Carlos A. González
  • Alina Diaz
  • Lila Castellanos
  • Aniel Sanchez
  • Lazaro Betancourt
  • Vladimir Besada
  • Luis J. González
  • Hilda Garay
  • Roberto Gómez
  • Daniel E. Gómez
  • Daniel F. Alonso
  • Phillipe Perrin
  • Jean-Yves Renualt
  • Hugo Sigman
  • Luis Herrera
  • Boris Acevedo
Article

DOI: 10.1007/s11010-011-0950-y

Cite this article as:
Perea, S.E., Baladron, I., Garcia, Y. et al. Mol Cell Biochem (2011) 356: 45. doi:10.1007/s11010-011-0950-y

Abstract

CK2 represents an oncology target scientifically validated. However, clinical research with inhibitors of the CK2-mediated phosphorylation event is still insufficient to recognize it as a clinically validated target. CIGB-300, an investigational peptide-based drug that targets the phosphoaceptor site, binds to a CK2 substrate array in vitro but mainly to B23/nucleophosmin in vivo. The CIGB-300 proapoptotic effect is preceded by its nucleolar localization, inhibition of the CK2-mediated phosphorylation on B23/nucleophosmin and nucleolar disassembly. Importantly, CIGB-300 shifted a protein array linked to apoptosis, ribosome biogenesis, cell proliferation, glycolisis, and cell motility in proteomic studies which helped to understand its mechanism of action. In the clinical ground, CIGB-300 has proved to be safe and well tolerated in a First-in-Human trial in women with cervical malignancies who also experienced signs of clinical benefit. In a second Phase 1 clinical trial in women with cervical cancer stage IB2/II, the MTD and DLT have been also identified in the clinical setting. Interestingly, in cervical tumors the B23/nucleophosmin protein levels were significantly reduced after CIGB-300 treatment at the nucleus compartment. In addition, expanded use of CIGB-300 in case studies has evidenced antitumor activity when administered as compassional option. Collectively, our data outline important clues on translational and clinical research from this novel peptide-based drug reinforcing its perspectives to treat cancer and paving the way to validate CK2 as a promising target in oncology.

Keywords

CIGB-300 Nucleophosmin Protein kinase CK2 Cell penetrating peptide Cancer targeted therapy 

Abbreviations

MTD

Maximal tolerated dose

DLT

Dose-limiting toxicity

CIGB-300-B

CIGB-300 conjugated to biotin

BFS

Bovine fetal serum

TBB

4,5,6,7-Tetrabromobenzotriazole

PBS

Phosphate buffer solution

RIPA

Radioimmunoprecipitation assay

HPV

Human papillomavirus

99Tc

Technetium-99

MRI

Magnetic resonance images

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Silvio E. Perea
    • 1
  • Idania Baladron
    • 1
  • Yanelda Garcia
    • 1
  • Yasser Perera
    • 1
  • Adlin Lopez
    • 5
  • Jorge L. Soriano
    • 5
  • Noyde Batista
    • 5
  • Aley Palau
    • 5
  • Ignacio Hernández
    • 6
  • Hernán Farina
    • 8
  • Idrian Garcia
    • 1
  • Lidia Gonzalez
    • 1
  • Jeovanis Gil
    • 1
  • Arielis Rodriguez
    • 1
  • Margarita Solares
    • 2
  • Agueda Santana
    • 3
  • Marisol Cruz
    • 1
  • Matilde Lopez
    • 1
  • Carmen Valenzuela
    • 1
  • Osvaldo Reyes
    • 1
  • Pedro A. López-Saura
    • 1
  • Carlos A. González
    • 4
  • Alina Diaz
    • 4
  • Lila Castellanos
    • 1
  • Aniel Sanchez
    • 1
  • Lazaro Betancourt
    • 1
  • Vladimir Besada
    • 1
  • Luis J. González
    • 1
  • Hilda Garay
    • 1
  • Roberto Gómez
    • 7
  • Daniel E. Gómez
    • 8
  • Daniel F. Alonso
    • 8
  • Phillipe Perrin
    • 9
  • Jean-Yves Renualt
    • 9
  • Hugo Sigman
    • 7
  • Luis Herrera
    • 1
  • Boris Acevedo
    • 1
  1. 1.Center for Genetic Engineering and Biotechnology (CIGB)HavanaCuba
  2. 2.Gyneco-obstetric Hospital “Clodomira Acosta Ferrales”HavanaCuba
  3. 3.Gyneco-obstetric Hospital “10 de Octubre”HavanaCuba
  4. 4.National Center for ToxicologyHavanaCuba
  5. 5.General Hospital “Hermanos Ameijeiras”HavanaCuba
  6. 6.Isotopes CenterHavanaCuba
  7. 7.ELEA LaboratoriosBuenos AiresArgentina
  8. 8.National University of QuilmesBuenos AiresArgentina
  9. 9.Chemo GroupParisFrance

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