HDAC inhibitor‐based therapies: Can we interpret the code?

New, Maria I.; Olzscha, Heidi; Thangué, Nicholas B. La

doi:10.1016/j.molonc.2012.09.003

Cited by 275 publications

(223 citation statements)

References 206 publications

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“…Interestingly, evidence from several reports indicates that HDAC levels are increased in certain cancer types (22)(23)(24). In addition, HDAC inhibitors have been reported to enhance the acetylation of histones, in tumor cells (25). Unlike other cytostatic-type compounds, HDAC inhibitors have been reported to exert much lower cytoxicity on normal cells, than on cancer cells.…”

Section: Hdac Inhibitors As Anti-cancer Agentsmentioning

confidence: 99%

Histone Deacetylases as New Therapeutic Targets in Triple-negative Breast Cancer: Progress and Promises

2017

CGP

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Section: Hdac Inhibitors As Anti-cancer Agentsmentioning

confidence: 99%

Histone Deacetylases as New Therapeutic Targets in Triple-negative Breast Cancer: Progress and Promises

2017

CGP

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“…This was also observed in our study since accumulation of G2-phase cells documented after 24 hours of incubation with 2 and 5 mmol/l of NaBu was followed with disappearance of G2-phase cells and accumulation of dead cells after 48 hours of incubation. Unlike HDACi-mediated G1-phase arrest, the underlying mechanisms responsible for HDACi-mediated G2-phase arrest are poorly understood (New et al 2012). It has been proposed that induction of an HDACi-associated G2 checkpoint might be related to hyperacetylation of pericentric heterochromatin and loss of this checkpoint can result in abnormal chromosomal segregation and nuclear fragmentation (Taddei et al 2005).…”

Section: Discussionmentioning

confidence: 99%

ABT-737 accelerates butyrate-induced death of HL-60 cells. Involvement of mitochondrial apoptosis pathway

Stefanikova

Kliková²,

Hatok³

et al. 2013

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Abstract. The aim of presented study was to determine effect of NaBu in combination with ABT-737 on cell survival of leukemic cell line HL-60. In addition, analysis of molecular mechanism of NaBu action with a focus on mitochondrial apoptosis was performed. Both NaBu and ABT-737 are inducing death of HL-60 cells with different kinetics. ABT-737-induced cell death is fast while NaBu-induced death preceded by cell cycle arrest in G2 phase is rather slow. Cell viability was significantly decreased after 48 hours of incubation with 2 and 5 mmol/l of NaBu while it was significantly decreased after 24 hours of incubation with 1 μmol/l of ABT-737 combined with 2 and 5 mmol/l of NaBu. Incubation of HL-60 cells with NaBu was associated with increased level of pro-apoptotic protein BIM EL and decreased levels of anti-apoptotic proteins of Bcl-2 family as well as GRP78 involved in ER stress signalling. It seems that ABT-737 accelerates NaBu-induced death of HL-60 cells due to mitochondrial apoptosis resulting from ABT-737-mediated inhibition of functions and NaBu-induced decrease of the levels of anti-apoptotic Bcl-2 family proteins as well as due to accelerated decrease of GRP78 observed after the treatment of cells with combination of NaBu and ABT-737. The effect of combination of both drugs on survival of HL-60 cells seems to be synergistic at high concentrations of NaBu (2 and 5 mmol/) while it is rather antagonistic at concentrations of NaBu less than 1 mmol/l. Finally, it might be assumed that NaBu is capable to induce cell death with mechanisms independent from mitochondrial apoptosis.

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“…There are four families of HDACs and HDAC inhibitors have varying inhibitory activity against each family which may be important in their relative efficacy against a variety of tumor types. 19 Vorinostat, panobinostat, and romidepsin have all been demonstrated to have activity in cutaneous T-cell lymphoma (CTCL) and both vorinostat and romidepsin are now licensed for this disease in a relapsed/refractory setting. [20][21][22] For PTCL, romidepsin has the most mature clinical data.…”

Section: Histone Deacetylase Inhibitorsmentioning

confidence: 99%

New Therapies in T-cell Lymphoma

2014

Lymphoma and Chronic Lymphocytic Leukemias

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T-cell lymphomas represent 10-12% of all patients with non-Hodgkin lymphoma (NHL) in the Western world. When cutaneous T-cell lymphoma (CTCL) is excluded, peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), anaplastic large-cell lymphoma (ALCL), and angioimmunoblastic T-cell lymphoma (AITL) represent the overwhelming majority of patients in this population. These diseases remain a great challenge to treat. They are characterized by an aggressive presentation, extranodal disease, paraneoplastic phenomena, and resistance to standard chemotherapeutics. With the rapid development of new molecular gene profiling techniques, it is highly likely that these diseases will be subclassified by molecular abnormalities in the future. An evolving understanding of the tumor molecular pathogenesis will undoubtedly lead to further novel targeted therapies. Immunoconjugates, such as brentuximab vedotin (BV), have provided outstanding responses in relapsed, refractory CD30-positive ALCL. Histone deacetylase (HDAC) inhibitors have shown activity in PTCL and are potentially synergistic with proteasome inhibitors. Denileukin diftitox is an interesting recombinant DNA fusion protein linking fragments of the diphtheria toxin to interleukin-2 (IL-2) that is tested in clinical trials. Crizotinib, a highly specific anaplastic lymphoma kinase (ALK) inhibitor, has shown great promise in small number of patients with ALK-positive ALCL; the future of patients with this disorder looks very promising. Biomarker-driven chemotherapeutics is becoming a critical part of the state-of-the-art treatment in early-and late-phase clinical trials. It is crucial that future trials include sensible biomarker-based designs when future treatments are used in these challenging disorders.KEY WORDS: T cell lymphoma, angioimmunoplastic lymphoma, anaplastic large cell lymphoma, brentuximab, crizotinib disclose no potential conflicts of interest.COPYRIGHT: © the authors, publisher and licensee Libertas academica Limited. this is an open-access article distributed under the terms of the Creative Commons CC-By-nC 3.0 License. CORRESPONDENCE: graham.collins@ouh.nhs.uk this paper was subject to independent, expert peer review by a minimum of two blind peer reviewers. all editorial decisions were made by the independent academic editor. all authors have provided signed confirmation of their compliance with ethical and legal obligations including (but not limited to) use of any copyrighted material, compliance with ICMJE authorship and competing interests disclosure guidelines and, where applicable, compliance with legal and ethical guidelines on human and animal research participants. provenance: the authors were invited to submit this paper.

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HDAC inhibitor‐based therapies: Can we interpret the code?

Cited by 275 publications

References 206 publications

Histone Deacetylases as New Therapeutic Targets in Triple-negative Breast Cancer: Progress and Promises

Histone Deacetylases as New Therapeutic Targets in Triple-negative Breast Cancer: Progress and Promises

ABT-737 accelerates butyrate-induced death of HL-60 cells. Involvement of mitochondrial apoptosis pathway

New Therapies in T-cell Lymphoma

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