A phase 1 study of bortezomib and romidepsin in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, indolent B-cell lymphoma, peripheral T-cell lymphoma, or cutaneous T-cell lymphoma

Holkova, Beata; Yazbeck, Victor; Kmieciak, Maciej; Bose, Prithviraj; Ma, Shuo; Kimball, Amy; Tombes, Mary Beth; Shrader, Ellen; Wan, Wen; Weir-Wiggins, Caryn; Singh, Amanda; Hogan, Kevin T.; Conine, Sarah; Sankala, Heidi; Roberts, John D.; Shea, Thomas C.; Grant, Steven

doi:10.1080/10428194.2016.1276287

Cited by 20 publications

(9 citation statements)

References 31 publications

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“…Sulforaphane can directly bind to and inhibit 26S and 20S proteasome subunits, leading to cell cycle arrest and apoptosis in multiple myeloma cell lines 23 . Since drugs targeting the proteasome 26S subunit, such as bortezomib, have been used successfully in combination with various chemotherapeutics and HDACi to treat myeloma and various types of LSA in human, 45,46 the downregulation of proteasome subunits after a week of supplementation with SFN could represent an important anticancer strategy to be explored in future studies.…”

Section: Discussionmentioning

confidence: 99%

Prospective evaluation of the lymph node proteome in dogs with multicentric lymphoma supplemented with sulforaphane

Parachini‐Winter

Bracha

Ramsey

et al. 2020

Veterinary Internal Medicne

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Background: Lymphoma (LSA) is a common malignancy in dogs. Epigenetic changes are linked to LSA pathogenesis and poor prognosis in humans, and LSA pathogenesis in dogs. Sulforaphane (SFN), an epigenetic-targeting compound, has recently gained interest in relation to cancer prevention and therapy. Objective: Examine the impact of oral supplementation with SFN on the lymph node proteome of dogs with multicentric LSA. Animals: Seven client-owned dogs with multicentric LSA. Methods: Prospective, nonrandomized, noncontrolled study in treatment-naïve dogs with intermediate or large cell multicentric LSA. Lymph node cell aspirates were obtained before and after 7 days of oral supplementation with SFN, and analyzed via label-free mass spectrometry, immunoblots, and Gene Set Enrichment Analysis. Results: There was no clinical response and no adverse events attributed to SFN. For individual dogs, the expression of up to 650 proteins changed by at least 2-fold (range, 2-100) after supplementation with SFN. When all dogs where analyzed together, 14 proteins were significantly downregulated, and 10 proteins were significantly upregulated after supplementation with SFN (P < .05). Proteins and gene sets impacted by SFN were commonly involved in immunity, response to oxidative stress, gene transcription, apoptosis, protein transport, maturation and ubiquitination. Conclusions and Clinical Importance: Sulforaphane is associated with major changes in the proteome of neoplastic lymphocytes in dogs.

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Section: Discussionmentioning

confidence: 99%

Prospective evaluation of the lymph node proteome in dogs with multicentric lymphoma supplemented with sulforaphane

Parachini‐Winter

Bracha

Ramsey

et al. 2020

Veterinary Internal Medicne

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“…Early results seem promising. Nevertheless, the larger cohorts are awaited for more objective discussion (96)(97)(98)(99)(100)(101).…”

Section: Most Current Trials In R/r Ptclmentioning

confidence: 99%

Nodal and extranodal peripheral T/NK-cell neoplasms: Current aspects

Petković¹,

Popović²,

Džunić³

et al. 2020

Acta fac medic Naissensis

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Peripheral T/NK-cell lymphomas (PTCL) are rare, bizarre, and extremely diverse cancers. The disease is prone to relapse with a high level of chemorefractoriness leading to a poor outcome. Almost 70% of patients will experience relapse, with a median 5-year overall survival (OS) in approximately 30%. Upfront management of PTCL has been extrapolated from the treatment paradigm for aggressive B-NHL. However, universally accepted induction is rather palliative than curative. Regardless of the maximal reinforcement of upfront management, only event-free survival has been influenced but not the OS. All actual guidelines emphasize the importance of the autologous stem cell transplantation (auto-SCT) as a consolidation of first major response. The allogeneic SCT (allo-SCT) is not evidence-based part of upfront management. Nevertheless, its use is justified in the relapsed/refractory setting. Unfortunately, the vast majority of patients are not candidates for aggressive treatment modalities making the recommended paradigm as limited feasible. Regarding such a situation, novel compounds are warranted. Although presented data indicate ominous prognosis in PTCL, it is important to denote that there has been evidence-based improvement in the treatment paradigm by the introduction of L-Asparaginase and targeted therapy for CD30+ PTCL. In this sense, a considerable number of new compounds entered early phase trials and gave promising results. All lights have been focused on upcoming results given the fact that at the moment we have not much to offer to the patients who have relapsed or were primary refractory.

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“…In line with this, the isotype-selective HDACis include the benzamides entinostat (MS-275, SNDX-275) and mocetinostat (MGCD0103) (Fournel et al, 2008; Vannini et al, 2004), the hydroxamic acid derivative rocilinostat (ACY-1215) (Santo et al, 2012), and the cyclic peptide romidepsin, which show preference for HDAC1-6-8, HDAC6, and HDAC1-2, respectively (Lemoine and Younes, 2010). Several HDACis like vorinostat, mocetinostat, and entinostat can be administered orally; conversely, other agents like romidepsin are given intravenously (Batlevi et al, 2016; Mann et al, 2007; Younes et al, 2011; Holkova et al, 2017). By inhibiting the catalytic activity of their target HDAC(s), these compounds impair the formation of HDAC–substrate complexes, thus altering the transcriptomic pattern of the malignant cells as well as the activity of non‐histone proteins, ultimately leading to growth arrest, differentiation, and induction of apoptosis (Qiu et al, 2000).…”

Section: Targeting Eraser Epigenetic Enzymes: Hdac Inhibitorsmentioning

confidence: 99%

Recent Advances in the Targeting of Epigenetic Regulators in B-Cell Non-Hodgkin Lymphoma

et al. 2019

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In the last 10 years, major advances have been made in the diagnosis and development of selective therapies for several blood cancers, including B-cell non-Hodgkin lymphoma (B-NHL), a heterogeneous group of malignancies arising from the mature B lymphocyte compartment. However, most of these entities remain incurable and current treatments are associated with variable efficacy, several adverse events, and frequent relapses. Thus, new diagnostic paradigms and novel therapeutic options are required to improve the prognosis of patients with B-NHL. With the recent deciphering of the mutational landscapes of B-cell disorders by high-throughput sequencing, it came out that different epigenetic deregulations might drive and/or promote B lymphomagenesis. Consistently, over the last decade, numerous epigenetic drugs (or epidrugs) have emerged in the clinical management of B-NHL patients. In this review, we will present an overview of the most relevant epidrugs tested and/or used so far for the treatment of different subtypes of B-NHL, from first-generation epigenetic therapies like histone acetyl transferases (HDACs) or DNA-methyl transferases (DNMTs) inhibitors to new agents showing selectivity for proteins that are mutated, translocated, and/or overexpressed in these diseases, including EZH2, BET, and PRMT. We will dissect the mechanisms of action of these epigenetic inhibitors, as well as the molecular processes underlying their lack of efficacy in refractory patients. This review will also provide a summary of the latest strategies being employed in preclinical and clinical settings, and will point out the most promising lines of investigation in the field.

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A phase 1 study of bortezomib and romidepsin in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, indolent B-cell lymphoma, peripheral T-cell lymphoma, or cutaneous T-cell lymphoma

Cited by 20 publications

References 31 publications

Prospective evaluation of the lymph node proteome in dogs with multicentric lymphoma supplemented with sulforaphane

Prospective evaluation of the lymph node proteome in dogs with multicentric lymphoma supplemented with sulforaphane

Nodal and extranodal peripheral T/NK-cell neoplasms: Current aspects

Recent Advances in the Targeting of Epigenetic Regulators in B-Cell Non-Hodgkin Lymphoma

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