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IFN-α potentiates the direct and immune-mediated antitumor effects of epigenetic drugs on both metastatic and stem cells of colorectal cancer.
Buoncervello, Maria; Romagnoli, Giulia; Buccarelli, Mariachiara; Fragale, Alessandra; Toschi, Elena; Parlato, Stefania; Lucchetti, Donatella; Macchia, Daniele; Spada, Massimo; Canini, Irene; Sanchez, Massimo; Falchi, Mario; Musella, Martina; Biffoni, Mauro; Belardelli, Filippo; Capone, Imerio; Sgambato, Alessandro; Vitiani, Lucia Ricci; Gabriele, Lucia.
Affiliation
  • Buoncervello M; Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
  • Romagnoli G; Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
  • Buccarelli M; Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
  • Fragale A; Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
  • Toschi E; Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
  • Parlato S; Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
  • Lucchetti D; Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, Rome, Italy.
  • Macchia D; Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
  • Spada M; Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
  • Canini I; Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
  • Sanchez M; Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
  • Falchi M; National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
  • Musella M; Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
  • Biffoni M; Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
  • Belardelli F; Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
  • Capone I; Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
  • Sgambato A; Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, Rome, Italy.
  • Vitiani LR; Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
  • Gabriele L; Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Oncotarget ; 7(18): 26361-73, 2016 May 03.
Article in En | MEDLINE | ID: mdl-27028869
Epigenetic alterations, including dysregulated DNA methylation and histone modifications, govern the progression of colorectal cancer (CRC). Cancer cells exploit epigenetic regulation to control cellular pathways, including apoptotic and metastatic signals. Since aberrations in epigenome can be pharmacologically reversed by DNA methyltransferase and histone deacetylase inhibitors, epigenetics in combination with standard agents are currently envisaged as a new therapeutic frontier in cancer, expected to overcome drug resistance associated with current treatments. In this study, we challenged this idea and demonstrated that the combination of azacitidine and romidepsin with IFN-α owns a high therapeutic potential, targeting the most aggressive cellular components of CRC, such as metastatic cells and cancer stem cells (CSCs), via tight control of key survival and death pathways. Moreover, the antitumor efficacy of this novel pharmacological approach is associated with induction of signals of immunogenic cell death. Of note, a previously undisclosed key role of IFN-α in inducing both antiproliferative and pro-apoptotic effects on CSCs of CRC was also found. Overall, these findings open a new frontier on the suitability of IFN-α in association with epigenetics as a novel and promising therapeutic approach for CRC management.
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Full text: 1 Database: MEDLINE Main subject: Neoplastic Stem Cells / Colorectal Neoplasms / Antineoplastic Combined Chemotherapy Protocols / Interferon-alpha Type of study: Prognostic_studies Limits: Animals / Humans Language: En Year: 2016 Type: Article

Full text: 1 Database: MEDLINE Main subject: Neoplastic Stem Cells / Colorectal Neoplasms / Antineoplastic Combined Chemotherapy Protocols / Interferon-alpha Type of study: Prognostic_studies Limits: Animals / Humans Language: En Year: 2016 Type: Article