INVESTIGADORES
FARINA Hernan Gabriel
artículos
Título:
CIGB-300, a synthetic peptide-based drug that targets the CK2 phosphoaceptor domain. Translational and clinical research.
Autor/es:
PEREA SE; BALADRON I, GARCIA Y, PERERA Y, LOPEZ A, SORIANO JL, BATISTA N, PALAU, A, HERNÁNDEZ I,; FARINA H; GARCIA I, GONZALEZ L, GIL J, RODRIGUEZ A, SOLARES M, SANTANA A, CRUZ M, LOPEZ M, VALENZUELA C, REYES O, LÓPEZ-SAURA PA, GONZÁLEZ CA, DIAZ A, CASTELLANOS L, SANCHEZ A, BETANCOURT L, BESADA V, GONZÁLEZ LJ, GARAY H; GÓMEZ R, GÓMEZ DE, ALONSO DF; PERRIN P, RENUALT JY, SIGMAN H, HERRERA L, ACEVEDO B.
Revista:
MOLECULAR AND CELLULAR BIOCHEMISTRY
Editorial:
SPRINGER
Referencias:
Lugar: Winnipeg; Año: 2011 vol. 356 p. 45 - 50
ISSN:
0300-8177
Resumen:
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.