Polycomb repressive complex 2 (PRC2) is known to regulate gene expression and chromatin structure as it methylates H3K27, resulting in gene silencing. Studies have shown that PRC2 has dual functions in oncogenesis that allow it to function as both an oncogene and a tumor suppressor. Because of this, nuanced strategies are necessary to promote or inhibit PRC2 activity therapeutically. Given the therapeutic vulnerabilities and associated risks in oncological applications, a structured literature review on PRC2 was conducted to showcase similar cofactor competitor inhibitors of PRC2. Key inhibitors such as Tazemetostat, GSK126, Valemetostat, and UNC1999 have shown promise for clinical use within various studies. Tazemetostat and GSK126 are both highly selective for wild-type and lymphoma-associated EZH2 mutants. Valemetostat and UNC1999 have shown promise as orally bioavailable and SAM-competitive inhibitors of both EZH1 and EZH2, giving them greater efficacy against potential drug resistance. The development of other PRC2 inhibitors, particularly inhibitors targeting the EED or SUZ12 subunit, is also being explored with the development of drugs like EED 226. This review aims to bridge gaps in the current literature and provide a unified perspective on promising PRC2 inhibitors as therapeutic agents in the treatment of lymphomas and solid tumors.
High-grade glioma is the most frequent and lethal primary tumor of the central nervous system. Despite advances in surgical, pharmacological, and cell-directed therapies, there have been no updates to the standard of care in over a decade. This cross-sectional study analyzes patient and trial data from 201 interventional trials completed between 2010 and 2023, encompassing 18,563 participants. Although we found that all trials reported participant age and sex, only 52% of trials reported participant demographics, resulting in 51% of total participant demographics being unreported. The majority of studies did not report ethnicity, with approximately 60% of participants unreported. Additionally, males were significantly underrepresented in trials, comprising 60% of participants despite representing 75% of glioblastoma patients. Improved demographic reporting has been observed since 2011; however, it is inconsistent. Furthermore, we cataloged the geographic diversity of trials across the United States and found significant coverage deserts in relatively rural, but highly affected, areas such as Montana and Maine. We found a wider distribution of trials in both urban and wealthier regions, which indicates extensive coverage gaps and decreased access to participation for patients of a lower socioeconomic status.