Tazemetostat: First Approval

Hoy, Sheridan M.

doi:10.1007/s40265-020-01288-x

Cited by 232 publications

(177 citation statements)

References 19 publications

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“…Furthermore, pharmacological inhibition of EZH2 in BAP1 -mutant MPM cell lines abrogated their growth in vitro and in vivo, suggesting that EZH2 could represent a genotype-specific vulnerability in MPM [ 130 ]. In strong support of these findings, Tazemostat, a first-in-class small-molecule inhibitor of EZH2 received accelerated FDA approval in January 2020 for the treatment of locally advanced or metastatic epithelioid sarcoma [ 131 ]. More importantly, it is currently undergoing clinical development for use in other tumor types, including MPM.…”

Section: Genomics Of Malignant Pleural Mesotheliomamentioning

confidence: 99%

Genomics and Functional Genomics of Malignant Pleural Mesothelioma

Çakıroğlu

Şentürk

2020

IJMS

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Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the mesothelial cells lining the pleural surface of the chest wall and lung. The etiology of MPM is strongly associated with prior exposure to asbestos fibers, and the median survival rate of the diagnosed patients is approximately one year. Despite the latest advancements in surgical techniques and systemic therapies, currently available treatment modalities of MPM fail to provide long-term survival. The increasing incidence of MPM highlights the need for finding effective treatments. Targeted therapies offer personalized treatments in many cancers. However, targeted therapy in MPM is not recommended by clinical guidelines mainly because of poor target definition. A better understanding of the molecular and cellular mechanisms and the predictors of poor clinical outcomes of MPM is required to identify novel targets and develop precise and effective treatments. Recent advances in the genomics and functional genomics fields have provided groundbreaking insights into the genomic and molecular profiles of MPM and enabled the functional characterization of the genetic alterations. This review provides a comprehensive overview of the relevant literature and highlights the potential of state-of-the-art genomics and functional genomics research to facilitate the development of novel diagnostics and therapeutic modalities in MPM.

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Section: Genomics Of Malignant Pleural Mesotheliomamentioning

confidence: 99%

Genomics and Functional Genomics of Malignant Pleural Mesothelioma

Çakıroğlu

Şentürk

2020

IJMS

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“…In small cell lung cancer cells, SLFN11 expression is silenced by marked deposition of H3K27me3, leading to drug resistance and recurrence after long treatment of platinum-derivatives, yet reactivated by inhibition of EZH2 a methyltransferase for H3K27 [25]. EZH2 inhibitor, tazemetostat has recently been approved by FDA for the treatment of follicular lymphoma [47]. Moreover, its efficacy for DLBCL is being studied [47].…”

Section: Discussionmentioning

confidence: 99%

“…EZH2 inhibitor, tazemetostat has recently been approved by FDA for the treatment of follicular lymphoma [47]. Moreover, its efficacy for DLBCL is being studied [47].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic suppression of SLFN11 in germinal center B cells in the process of the dynamic expression change during B-cell development

Moribe¹,

Nishikori²,

Sasanuma

et al. 2020

Preprint

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Background SLFN11 enhances cellular toxicity of genotoxic anti-cancer agents, and its important role under physiological conditions has not been appreciated yet. Somatic hypermutations and class switch recombination that can cause physiological genotoxic stress arise in germinal center B cells (GCBs). GCBs are a major origin of B-cell lymphomas that are frequently treated by cytosine arabinoside, a genotoxic anti-cancer agent. Objective To clarify the expression profile of SLFN11 in different stages of B cells and B-cell lymphomas. Methods We analyzed the expression of SLFN11 by mining publicly available databases for different stages of normal B cells and various types of B-cell lymphoma lines and also by performing immunohistochemical staining of human lymph nodes. We investigated the effects of two epigenetic modifiers, an EZH2 inhibitor, tazemetostat (EPZ6438) and a histone deacetylase inhibitor, panobinostat (LBH589) on SLFN11 expression in B-cell lymphoma lines and examined the therapeutic efficacy of these epigenetic modifiers in the combination with cytosine arabinoside. Results SLFN11 expression was specifically low in GCBs compared to non-GCBs, which was consolidated by the immunohistochemical staining for SLFN11 with human lymph nodes. SLFN11 expression levels in B-cell lymphoma lines largely correlated to those of their normal counterparts. The epigenetic modifiers upregulated SLFN11 expression in GCB-derived lymphomas and made the lymphomas further susceptible to cytosine arabinoside. Conclusions The expression of SLFN11 may be epigenetically suppressed in GCBs and GCB-derived lymphomas. GCB-derived lymphomas with low SLFN11 expression can be treated by the combination of epigenetic modifiers and cytosine arabinoside.

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“…The loss of SMARCB1/INI1 protein in epithelioid sarcoma is tumor-promoting and is currently used in the clinic as a biomarker for differential diagnosis (18). More importantly, the loss of SMARCB1/INI1 leads to the deregulation of EZH2, and drugs targeting EZH2 have been proven successful in controlling tumor growth and are currently approved to be used in treating epithelioid sarcoma (19). Dedifferentiated liposarcoma is characterized by 12q13-15 amplifications.…”

Section: In Genomic Settingsmentioning

confidence: 99%

“…As mentioned above, different sarcomas vary greatly in genomic alterations. Based on these alterations, multiple targeted therapies have been developed and approved such as pazopanib (21), anlotinib (22), and most recently tazemetostat (19). Pazopanib and anlotinib are both multi-target tyrosine kinase inhibitors.…”

Section: Targeted Therapymentioning

confidence: 99%

Heterogeneity of Soft Tissue Sarcomas and Its Implications in Targeted Therapy

Wei

Zhang

et al. 2020

Front. Oncol.

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Soft tissue sarcomas are a set of malignancies of mesenchymal origin. Due to the rarity and similarity in clinical presentation, they are grouped together and treated similarly in clinic. The response rates for current chemotherapy are around 20% and the median overall survival for advanced soft tissue sarcoma are less than 2 years. Thus, the current strategy with identical treatment for all soft tissue sarcomas is far from satisfactory. In this study, we first reviewed the current clinical and genomic findings of soft tissue sarcoma, paying special attention to the heterogeneities among different tumors. Then we reviewed the state-of-art understanding of targeted therapy in soft tissue sarcoma. We observed tremendous heterogeneity both in clinical and genomic settings between different tumors. Individualized treatment plans demonstrated better response and disease control and should be advocated. In summary, heterogeneity of soft tissue sarcomas requires the development of individualized treatment plans such as targeted therapy.

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Tazemetostat: First Approval

Cited by 232 publications

References 19 publications

Genomics and Functional Genomics of Malignant Pleural Mesothelioma

Genomics and Functional Genomics of Malignant Pleural Mesothelioma

Epigenetic suppression of SLFN11 in germinal center B cells in the process of the dynamic expression change during B-cell development

Heterogeneity of Soft Tissue Sarcomas and Its Implications in Targeted Therapy

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