Belinostat for the treatment of relapsed or refractory peripheral T-cell lymphoma

Campbell, Peter M.; Thomas, Christan M.

doi:10.1177/1078155216634178

Cited by 49 publications

(25 citation statements)

References 22 publications

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“…It exhibited nanomolar inhibition against HDACI, II, and IV (Chowdhury et al, 2011). The clinical data from relapsed/refractory PTCL patients shows that belinostat, with high efficacy and low toxicity is an ideal drug for cancer treatment (Campbell and Thomas, 2017). With promising results, belinostat was approved for sale in 2014 for the treatment of relapsed or refractory PTCL (Poole, 2014).…”

Section: Belinostat (Pxd101)mentioning

confidence: 99%

Recent Update of HDAC Inhibitors in Lymphoma

Chen

Sethy

Liou

2020

Front. Cell Dev. Biol.

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Modulating epigenetic modification has been recognized for over a decade as an effective therapeutic approach to cancer and many studies of histone deacetylase (HDAC), one of the best known epigenetic modulators, have been published. HDAC modulates cell proliferation and angiogenesis and plays an essential role in cell growth. Research shows that up-regulated HDACs are present in many cancer types and synthetic or natural HDAC inhibitors have been used to silence overregulated HDACs. Inhibiting HDACs may cause arrest of cell proliferation, angiogenesis reduction and cell apoptosis. Recent studies indicate that HDAC inhibitors can provide a therapeutic effect in various cancers, such as B-cell lymphoma, leukemia, multiple myeloma and some virus-associated cancers. Some evidence has demonstrated that HDAC inhibitors can increase the expression of immune-related molecules leading to accumulation of CD8 + T cells and causing unresponsive tumor cells to be recognized by the immune system, reducing tumor immunity. This may be a solution for the blockade of PD-1. Here, we review the emerging development of HDAC inhibitors in various cancer treatments and reduction of tumor immunity.

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Section: Belinostat (Pxd101)mentioning

confidence: 99%

Recent Update of HDAC Inhibitors in Lymphoma

Chen

Sethy

Liou

2020

Front. Cell Dev. Biol.

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“…Overexpression of HDACs are observed in many cancer types, including prostate, gastric, and endometrial cancers [36]. Currently, three HDAC inhibitors are approved by the FDA: vorinostat (also known as SAHA) for the treatment of cutaneous T cell lymphoma [36], belinostat for the treatment of peripheral T cell lymphoma [37] and romidepsin for the treatment of both cutaneous and peripheral T-cell lymphoma [38].…”

Section: Epigenetic Regulationmentioning

confidence: 99%

Epigenetics and Sphingolipid Metabolism in Health and Disease

et al. 2018

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Sphingolipids represent one of the major classes of bioactive lipids. Studies of sphingolipids have intensified in the past several years, revealing their roles in nearly all cell biological processes. In addition, epigenetic regulation has gained substantial interest due to its role in controlling gene expression and activity without changing the genetic code. In this review, we first introduce a brief background on sphingolipid biology, highlighting its role in pathophysiology. We then illustrate the concept of epigenetic regulation, focusing on how it affects the metabolism of sphingolipids. We further discuss the roles of bioactive sphingolipids as epigenetic regulators themselves. Overall, a better understanding of the relationship between epigenetics and sphingolipid metabolism may help to improve the development of sphingolipid-targeted therapeutics.

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“…Belinostat (C 15 H 14 N 2 O 4 S) has a small molecular structure (318.35 g/mol) with moderate solubility (0.08 mg/mL at pH 7.4), properties that make it a suitable drug candidate. However, the half-life of belinostat is only 1.1 h [ 8 ]. It is imperative to develop a method to prolong the half-life of belinostat.…”

Section: Introductionmentioning

confidence: 99%

Prolonging the Half-Life of Histone Deacetylase Inhibitor Belinostat via 50 nm Scale Liposomal Subcutaneous Delivery System for Peripheral T-Cell Lymphoma

Cheng

Weng

Chuang

et al. 2020

Cancers

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Lymph node metastasis is an aggressive condition characterized by poor treatment outcomes and low overall survival. Belinostat is a novel histone deacetylase (HDAC) inhibitor approved by the Food and Drug Administration (FDA) for the treatment of relapsed peripheral T-cell lymphoma (PTCL). However, the major problem is that belinostat has a short half-life of 1.1 h. In this study, we successfully prepared 50 nm liposomal colloids, which showed a controlled release pattern and excellent pharmacokinetics. The results showed that the particle size of liposomes consisting of dioleoylphosphatidylcholine (DOPC) was larger than that of those consisting of dioleoylglycerophosphoserine (DOPS). In terms of release kinetics of belinostat, the free drug was rapidly released and showed lower area under curve (AUC) exposure for in vivo pharmacokinetics. When liposomal formulations were employed, the release pattern was fitted with Hixson–Crowell models and showed sustained release of belinostat. Moreover, HuT-78 cells were able to take up all the liposomes in a concentration-dependent manner. The safety assessment confirmed hemocompatibility, and the platelet count was increased. Furthermore, the liposomes consisting of DOPC or DOPS had different behavior patterns, and their delivery to lymphatic regions should be thoroughly investigated in the future.

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Belinostat for the treatment of relapsed or refractory peripheral T-cell lymphoma

Cited by 49 publications

References 22 publications

Recent Update of HDAC Inhibitors in Lymphoma

Recent Update of HDAC Inhibitors in Lymphoma

Epigenetics and Sphingolipid Metabolism in Health and Disease

Prolonging the Half-Life of Histone Deacetylase Inhibitor Belinostat via 50 nm Scale Liposomal Subcutaneous Delivery System for Peripheral T-Cell Lymphoma

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