Tazverik (tazemetostat)

For nearly twenty years, platinum-pemetrexed chemotherapy has persisted as the unchanged standard treatment; although recent progress in immunotherapy has modestly disrupted this therapeutic plateau, survival outcomes remain disappointingly limited...Preclinical and early clinical data demonstrate that EZH2 inhibitors-including tazemetostat, valemetostat, GSK126, EPZ011989, tulmimetostat, and novel PROTAC-based degraders such as MS1943-can suppress tumor progression, modulate the tumor immune microenvironment, and restore therapeutic sensitivity...Further understanding the dual canonical and non-canonical roles of EZH2 in tumor biology will be key to optimizing targeted and combinatorial treatment strategies. Future research should focus on translating EZH2 inhibition into clinical benefit, identifying predictive biomarkers of response, and exploring rational combinations with chemotherapy, targeted drugs, or immunotherapy to improve survival outcomes in mesothelioma patients.

P2, N=10, Active, not recruiting, University of Florida | Trial completion date: Apr 2026 --> Dec 2026

DOX-resistant breast cancer cell models were established and treated with the EZH2 inhibitors tazemetostat or GSK126, alone or in combination with DOX. EZH2 is a critical determinant of DOX resistance in breast cancer by sustaining DNA damage tolerance and metabolic homeostasis. Pharmacological targeting of EZH2 in combination with DOX represents a rational strategy to overcome chemoresistance in breast cancer.

Pharmacological inhibitors of EZH2, including tazemetostat, have shown promise in preclinical melanoma models by restoring antigen presentation, enhancing CD8+ T-cell infiltration, and reversing transcriptional programs associated with immune resistance. This review aims to summarize the role of EZH2 in the molecular pathogenesis of ALM, emphasizing its contributions to epigenetic regulation, tumor plasticity, and immune escape, and discusses emerging therapeutic strategies targeting EZH2-mediated pathways to improve outcomes for this aggressive melanoma subtype.

Notably, TZM monotherapy inhibited tumor growth in both FN- and FP-RMSCRR xenografts, uncovering a therapy-induced vulnerability. Our integrative multi-omics analysis reveals EZH2-dependent molecular programs underpinning radioresistance and supports EZH2 targeting as a rational radiosensitizing and therapeutic strategy in RMS, including recurrent and RT-refractory disease.

Valemetostat, which inhibits EZH1/2, as well as tazemetostat in combination with other drugs have been subject of recent research. The purpose of this article is to review the role of EZH2 in normal B cell differentiation and in the pathogenesis of B-Cell lymphomas.

We identified a novel ACSS2-H3K9ac-HK2 signaling axis that is characteristically activated in EZH2-non-mutant solid tumors and drives metabolic reprogramming and resistance to EZH2 inhibition.

Notably, we further found that the status of NRF1 expression affected the sensitivity of human cancer cells to EZH2is, including GSK343 and tazemetostat. In conclusion, our findings reveal that NRF1 is a dominant cause of EZH2 overexpression in human cancers and that NRF1 overexpression increases the sensitivity of cancer cells to EZH2is. Active NRF1 and EZH2 expression may be a useful combined predictor for the treatment of cancers with EZH2is.

P1, N=35, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Sep 2026 --> Dec 2026 | Trial primary completion date: Mar 2026 --> Sep 2025

Extra-CNS metastatic meningiomas pose significant diagnostic and therapeutic challenges. High-grade meningiomas are more likely to metastasize; early detection of metastatic spread is challenging. Our findings highlight the need for a multidisciplinary approach with close follow-up, especially in recurrent or high-grade meningiomas with distinct mutations.

Treatments include surgery, radiation, and chemotherapy, with ongoing trials investigating agents like cetuximab, cisplatin, and Tazemetostat. Tazemetostat, targeting KMT2D-related DNA (deoxyribonucleic acid) methylation, and cetuximab, targeting the PIK3CA signaling cascade, may offer therapeutic benefits. Further research on mutation-specific therapies could improve treatment strategies.

P=N/A, N=0, Withdrawn, Ipsen | N=63 --> 0 | Not yet recruiting --> Withdrawn