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

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 sit...

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Detalles Bibliográficos
Autores: Perea, Silvio E., Baladron, Idania, Garcia, Yanelda, Perera, Yasser, Lopez, Adlin, Soriano, Jorge L., Batista, Noyde, Palau, Aley, Hernández, Ignacio, Farina, Hernán Gabriel, Garcia, Idrian, Gonzalez, Lidia, Gil, Jeovanis, Rodriguez, Arielis, Solares, Margarita, Santana, Agueda, Cruz, Marisol, Lopez, Matilde, Valenzuela, Carmen, Reyes, Osvaldo, López Saura, Pedro A., González, Carlos A., Diaz, Alina, Castellanos, Lila, Sanchez, Aniel, Betancourt, Lazaro, Besada, Vladimir, González, Luis J., Garay, Hilda, Gómez, Roberto, Gomez, Daniel Eduardo, Alonso, Daniel Fernando, Perrin, Phillipe, Renualt, Jean Yves, Sigman, Hugo, Herrera, Luis, Acevedo, Boris
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2011
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/188799
Acceso en línea:http://hdl.handle.net/11336/188799
Access Level:acceso abierto
Palabra clave:CANCER TARGETED THERAPY
CELL PENETRATING PEPTIDE
CIGB-300
NUCLEOPHOSMIN
PROTEIN KINASE CK2
https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
Descripción
Sumario: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.

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