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Romidepsin and Afatinib Abrogate Jak-Signal Transducer and Activator of Transcription Signaling and Elicit Synergistic Antitumor Effects in Cutaneous T-Cell Lymphoma
Shih, Bobby (Columbia University)
Ma, Cindy (Columbia University)
Rodriguez Cortes, Jose (Columbia University)
Reglero, Clara (Columbia University)
Miller, Hannah I. (Columbia University)
Aidan Quinn, Stuart (Columbia University)
Albero Gallego, Robert (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Laurent, Anouchka (Columbia University)
Mackey, Adam (Columbia University)
Ferrando, Adolfo A. (Columbia University Medical Center)
Geskin, Larisa (Columbia University Medical Center)
Palomero, Teresa (Columbia University Medical Center)

Fecha: 2024
Resumen: Cutaneous T-cell lymphomas are mature lymphoid neoplasias resulting from the malignant transformation of skin-resident T-cells. A distinctive clinical feature of cutaneous T-cell lymphomas is their sensitivity to treatment with histone deacetylase inhibitors. However, responses to histone deacetylase inhibitor therapy are universally transient and noncurative, highlighting the need for effective and durable drug combinations. In this study, we demonstrate that the combination of romidepsin, a selective class I histone deacetylase inhibitor, with afatinib, an EGFR family inhibitor, induces strongly synergistic antitumor effects in cutaneous T-cell lymphoma models in vitro and in vivo through abrogation of Jak-signal transducer and activator of transcription signaling. These results support a previously unrecognized potential role for histone deacetylase inhibitor plus afatinib combination in the treatment of cutaneous T-cell lymphomas.
Nota: Altres ajuts: National Cancer Institute (1F31CA261153); National Institutes of Health/National Cancer Institute Cancer Center Support (P30CA013696)
Derechos: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. Creative Commons
Lengua: Anglès
Documento: Article ; recerca ; Versió publicada
Materia: Combination therapy ; Cutaneous T-cell lymphoma ; Preclinical models ; Romidepsin
Publicado en: The Journal of investigative dermatology, Vol. 144 Núm. 7 (July 2024) , p. 1579-1589.e8, ISSN 1523-1747

DOI: 10.1016/j.jid.2023.12.010
PMID: 38219917


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