Titel (eng)

High Efficacy and Drug Synergy of HDAC6-Selective Inhibitor NN-429 in Natural Killer (NK)/T-Cell Lymphoma

Autor*in

Harsimran Kaur Garcha   University of Toronto

Patrick T. Gunning   University of Toronto

Richard Moriggl   University of Veterinary Medicine Vienna

Elvin D. de Araujo   University of Toronto

Marco Herling   University of Leipzig

Satu M Mustjoki   University of Helsinki / Helsinki University Hospital Comprehensive Cancer Center

Heidi A. Neubauer   University of Veterinary Medicine Vienna

Sirano Dhe-Paganon   Dana-Farber Cancer Institute / Harvard Medical School

Daniel Pölöske   University of Veterinary Medicine Vienna

Susann Schönefeldt   University of Veterinary Medicine Vienna

Hyuk-Soo Seo   Dana-Farber Cancer Institute / Harvard Medical School

Pimyupa Manaswiyoungkul   University of Toronto

Abootaleb Sedighi   University of Toronto

Myint Myat Khine Aung   University of Veterinary Medicine Vienna

Fettah Erdogan   University of Toronto

Nabanita Nawar   University of Toronto

Helena Sorger   University of Veterinary Medicine Vienna

Verlag

MDPI

Beschreibung (eng)

NK/T-cell lymphoma (NKTCL) and γδ T-cell non-Hodgkin lymphomas (γδ T-NHL) are highly aggressive lymphomas that lack rationally designed therapies and rely on repurposed chemotherapeutics from other hematological cancers. Histone deacetylases (HDACs) have been targeted in a range of malignancies, including T-cell lymphomas. This study represents exploratory findings of HDAC6 inhibition in NKTCL and γδ T-NHL through a second-generation inhibitor NN-429. With nanomolar in vitro HDAC6 potency and high in vitro and in cellulo selectivity for HDAC6, NN-429 also exhibited long residence time and improved pharmacokinetic properties in contrast to older generation inhibitors. Following unique selective cytotoxicity towards γδ T-NHL and NKTCL, NN-429 demonstrated a synergistic relationship with the clinical agent etoposide and potential synergies with doxorubicin, cytarabine, and SNS-032 in these disease models, opening an avenue for combination treatment strategies.

Sprache des Objekts

Englisch

Datum

2022

Rechte

Dieses Werk bzw. dieser Inhalt steht unter einer
CC BY 4.0 - Creative Commons Namensnennung 4.0 International Lizenz.

CC BY 4.0 International

http://creativecommons.org/licenses/by/4.0/

Klassifikation

T-Cell Lymphoma; Histone Deacetylase Inhibitor; Refinement; Therapy; Tubulin; Cancer; Hdac6; Features; Assay

Mitglied in der/den Collection(s) (1)