Combinatorial strategies to potentiate the efficacy of HDAC inhibitors in fusion-positive sarcomas

Lanzi, Cinzia; Cassinelli, Giuliana

doi:10.1016/j.bcp.2022.114944

Cited by 12 publications

(7 citation statements)

References 204 publications

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“…Another study investigating the role of HDACi in increasing oxidative stress in RMS indicated that entinostat caused increased levels of intracellular ROS in xenograft mouse models (12). Although this study also highlighted cessation of tumor progression as a result of treatment using entinostat, it did not elucidate if the antineoplastic effects were solely attributed to the increase in intracellular ROS levels.…”

Section: Hdac Inhibitor-induced Modulation Of Oxidative Stressmentioning

confidence: 77%

A review of the therapeutic potential of histone deacetylase inhibitors in rhabdomyosarcoma

Selim,

Song,

Kumar

et al. 2023

Front. Oncol.

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This review aims to summarize the putative role of histone deacetylases (HDACs) in rhabdomyosarcoma (RMS) and the effects of HDAC inhibitors (HDACi) on RMS by elucidating and highlighting known oncogenic pathways, mechanisms of resistance, and the synergistic potential of histone deacetylase inhibitors. We searched two databases (PubMed and Google Scholar) for the keywords “Rhabdomyosarcoma, histone deacetylase, histone deacetylase inhibitors.” We excluded three publications that did not permit access to the full text to review and those that focus exclusively on pleiomorphic RMS in adults. Forty-seven papers met the inclusion criteria. This review highlights that HDACi induce cytotoxicity, cell-cycle arrest, and oxidative stress in RMS cells. Ultimately, HDACi have been shown to increase apoptosis and the cessation of embryonal and alveolar RMS proliferation in vivo and in vitro, both synergistically and on its own. HDACi contain potent therapeutic potential against RMS. This review discusses the significant findings and the biological mechanisms behind the anti-cancer effects of HDACi. Additionally, this review highlights important clinical trials assessing the efficacy of HDACi in sarcomas.

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Section: Hdac Inhibitor-induced Modulation Of Oxidative Stressmentioning

confidence: 77%

A review of the therapeutic potential of histone deacetylase inhibitors in rhabdomyosarcoma

Selim,

Song,

Kumar

et al. 2023

Front. Oncol.

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“…To explore therapeutic approaches for mesenchymal chondrosarcoma, our model was used as a preclinical platform to evaluate drug effects for mesenchymal chondrosarcoma. Although drug-sensitivity screening using a library of 334 compounds (Screening Committee of Anticancer Drugs [SCADS]) ( 47 ) failed to identify highly effective chemicals ( Supplemental Table 6 ), modulations of histone deacetylase functions have been emphasized in fusion gene-positive sarcomas as well as the Runx2 pathway in chondrosarcoma ( 48 , 49 ). We therefore tested HDAC inhibitors and identified panobinostat (Selleckchem) as an effective growth inhibitor.…”

Section: Resultsmentioning

confidence: 99%

HEY1-NCOA2 expression modulates chondrogenic differentiation and induces mesenchymal chondrosarcoma in mice

Tanaka¹,

Homme²,

Teramura³

et al. 2023

JCI Insight

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“…Preclinical studies have not found significant therapeutic benefits in solid tumors, including sarcomas. Nevertheless, in combination therapies based on HDACi, sarcomas were represented in most cases as an unclassified group [129]. More recent studies are now specifically examining individual sarcomas and attempting to identify meaningful combination therapies based on known/identified mechanisms: In Ewing sarcomas, we observed that CRISPR/Cas9 knockout of individual HDACs such as HDAC1 and HDAC2 inhibited the invasiveness of Ewing sarcomas and blocked local tumor growth of xenografts.…”

Section: Inhibition Of Key Players Of the Fusion-positive Interactomementioning

confidence: 90%

Drug Targeting of Chromosomal Translocations in Fusion-Positive Sarcoma

Richter¹

2023

Bone Tumours - A Comprehensive Review of Selected Topics

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Sarcomas are heterogeneous cancers of bone or soft tissue. They occur in children, adolescents, and young adults (AYAs). Herein, the subgroup of fusion-positive (FP) sarcomas is characterized by chromosomal rearrangements generating pathognomonic fusion transcripts and oncoproteins. In Ewing sarcoma (EwS), FP-rhabdomyosarcomas (FP-RMS) and synovial sarcomas (SyS), the most common and aggressive forms of sarcomas in childhood and adolescence, the oncogenic rearrangements involve transcription cofactors such as by FET-ETS, PAX3/7-FOXO1 or SS18-SSX fusion oncogenes in EwS, FP-RMS, or SyS, respectively causing widespread epigenetic rewiring and aberrant gene expression. Regardless of these translocations, few recurrent mutations are observed in these sarcomas that may contribute to disease; thus, it is of particular interest to consider the consequences of these translocations for tumor development. Results of current research examining the disease, analyzing, and classifying the role of associated rearrangements of chromatin, and investigating possibilities for tumor-specific intervention such as blocking the transcriptional activity of the fusion protein, or the processes caused by this activity are summarized here and some resulting therapeutic opportunities are presented.

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Combinatorial strategies to potentiate the efficacy of HDAC inhibitors in fusion-positive sarcomas

Cited by 12 publications

References 204 publications

A review of the therapeutic potential of histone deacetylase inhibitors in rhabdomyosarcoma

A review of the therapeutic potential of histone deacetylase inhibitors in rhabdomyosarcoma

HEY1-NCOA2 expression modulates chondrogenic differentiation and induces mesenchymal chondrosarcoma in mice

Drug Targeting of Chromosomal Translocations in Fusion-Positive Sarcoma

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