A novel approach to eliminate therapy-resistant mantle cell lymphoma: synergistic effects of Vorinostat with Palbociclib

Chaturvedi, Nagendra K.; Hatch, Nathan D.; Sutton, Garrett L.; Kling, Matthew J.; Vose, Julie M.; Joshi, Shantaram S.

doi:10.1080/10428194.2018.1520986

Cited by 12 publications

(7 citation statements)

References 32 publications

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“…Similar promising antitumoral effects were observed in multiple myeloma, anaplastic large-cell lymphoma, and mantle cell lymphoma, where palbociclib was also capable of overcoming ibrutinib resistance [29][30][31][32][33][34]. In a study with 17 relapsed mantle cell lymphoma patients, palbociclib achieved one complete remission (CR) and two partial responses (PR), five patients had a progression-free survival of at least one year with reduced tumor metabolism and proliferation [35].…”

Section: Palbociclibmentioning

confidence: 66%

Cyclin-Dependent Kinase Inhibitors in Hematological Malignancies—Current Understanding, (Pre-)Clinical Application and Promising Approaches

Richter

Schoenwaelder

Sender

et al. 2021

Cancers

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Genetically altered stem or progenitor cells feature gross chromosomal abnormalities, inducing modified ability of self-renewal and abnormal hematopoiesis. Cyclin-dependent kinases (CDK) regulate cell cycle progression, transcription, DNA repair and are aberrantly expressed in hematopoietic malignancies. Incorporation of CDK inhibitors (CDKIs) into the existing therapeutic regimens therefore constitutes a promising strategy. However, the complex molecular heterogeneity and different clinical presentation is challenging for selecting the right target and defining the ideal combination to mediate long-term disease control. Preclinical and early clinical data suggest that specific CDKIs have activity in selected patients, dependent on the existing rearrangements and mutations, potentially acting as biomarkers. Indeed, CDK6, expressed in hematopoietic cells, is a direct target of MLL fusion proteins often observed in acute leukemia and thus contributes to leukemogenesis. The high frequency of aberrancies in the retinoblastoma pathway additionally warrants application of CDKIs in hematopoietic neoplasms. In this review, we describe the preclinical and clinical advances recently made in the use of CDKIs. These include the FDA-approved CDK4/6 inhibitors, traditional and novel pan-CDKIs, as well as dual kinase inhibitors. We additionally provide an overview on molecular mechanisms of response vs. resistance and discuss open questions.

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Section: Palbociclibmentioning

confidence: 66%

Cyclin-Dependent Kinase Inhibitors in Hematological Malignancies—Current Understanding, (Pre-)Clinical Application and Promising Approaches

Richter

Schoenwaelder

Sender

et al. 2021

Cancers

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“…In addition, Vorinostat in combination with Palbociclib (selective inhibitor of cyclin-dependent kinase 4/6 involved in cell cycle progression) reduced MCL cell growth and induced apoptosis significantly by increasing histone H3 acetylation and inhibiting BCL-2 family members. Overexpression of BCL-2 family proteins attenuates apoptosis in tumor cells [69].…”

Section: Histone Deacetylationmentioning

confidence: 99%

Migration and Adhesion of B-Lymphocytes to Specific Microenvironments in Mantle Cell Lymphoma: Interplay between Signaling Pathways and the Epigenetic Landscape

Sadeghi

Wright

2021

IJMS

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Lymphocyte migration to and sequestration in specific microenvironments plays a crucial role in their differentiation and survival. Lymphocyte trafficking and homing are tightly regulated by signaling pathways and is mediated by cytokines, chemokines, cytokine/chemokine receptors and adhesion molecules. The production of cytokines and chemokines is largely controlled by transcription factors in the context of a specific epigenetic landscape. These regulatory factors are strongly interconnected, and they influence the gene expression pattern in lymphocytes, promoting processes such as cell survival. The epigenetic status of the genome plays a key role in regulating gene expression during many key biological processes, and it is becoming more evident that dysregulation of epigenetic mechanisms contributes to cancer initiation, progression and drug resistance. Here, we review the signaling pathways that regulate lymphoma cell migration and adhesion with a focus on Mantle cell lymphoma and highlight the fundamental role of epigenetic mechanisms in integrating signals at the level of gene expression throughout the genome.

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“…However, targeting epigenetic modification mechanisms is a relatively novel approach in MCL. Most of the preclinical studies have been centered on the evaluation of HDAC inhibitors, vorinostat being the main agent included in combination regimens with either proteasome, PI3K-AKT, CDK or BTK inhibitors [160]. From these different strategies, the combination of vorinostat plus BTZ has been evaluated in a phase 2 trial, but only a modest clinical activity was observed [161].…”

Section: Epigenetic Drugsmentioning

confidence: 99%

Management of Drug Resistance in Mantle Cell Lymphoma

Roué

Sola

2020

Cancers

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Mantle cell lymphoma (MCL) is a rare but aggressive B-cell hemopathy characterized by the translocation t(11;14)(q13;q32) that leads to the overexpression of the cell cycle regulatory protein cyclin D1. This translocation is the initial event of the lymphomagenesis, but tumor cells can acquire additional alterations allowing the progression of the disease with a more aggressive phenotype and a tight dependency on microenvironment signaling. To date, the chemotherapeutic-based standard care is largely inefficient and despite the recent advent of different targeted therapies including proteasome inhibitors, immunomodulatory drugs, tyrosine kinase inhibitors, relapses are frequent and are generally related to a dismal prognosis. As a result, MCL remains an incurable disease. In this review, we will present the molecular mechanisms of drug resistance learned from both preclinical and clinical experiences in MCL, detailing the main tumor intrinsic processes and signaling pathways associated to therapeutic drug escape. We will also discuss the possibility to counteract the acquisition of drug refractoriness through the design of more efficient strategies, with an emphasis on the most recent combination approaches.

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A novel approach to eliminate therapy-resistant mantle cell lymphoma: synergistic effects of Vorinostat with Palbociclib

Cited by 12 publications

References 32 publications

Cyclin-Dependent Kinase Inhibitors in Hematological Malignancies—Current Understanding, (Pre-)Clinical Application and Promising Approaches

Cyclin-Dependent Kinase Inhibitors in Hematological Malignancies—Current Understanding, (Pre-)Clinical Application and Promising Approaches

Migration and Adhesion of B-Lymphocytes to Specific Microenvironments in Mantle Cell Lymphoma: Interplay between Signaling Pathways and the Epigenetic Landscape

Management of Drug Resistance in Mantle Cell Lymphoma

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