Synovial Sarcoma

The recent patent data show how selective BRD9 degraders represent a significant step forward in terms of efficacy and selectivity, with promising results in preclinical models of acute myeloid leukemia (AML), synovial sarcoma (SS), and Huntington's disease (HD). Despite several critical issues, the selective degradation of this epigenetic target shows great potential to be an innovative therapeutic strategy.

The proliferative activity of SS xenografts could be assessed using quantitative parameters derived from IVIM and DCE-MRI.

To our knowledge, this is the first reported case of oral SS in Saudi Arabia or the surrounding region. The report underscores the importance of multidisciplinary collaboration in identifying clinically silent yet aggressive tumors.

This study demonstrates GFPT2's diagnostic utility in MESO, effectively overcoming tumour heterogeneity challenges. It distinguishes malignant mesothelial lesions from benign/borderline ones (RMH/WDPMT), differentiates epithelioid MESO from epithelioid malignances(NSCLC/HGSOC/EHE) and aids in sarcomatoid MESO versus spindle cell tumours (SFT/AF/SS/LMS/MPNST/sarcomatoid carcinoma), though limited for DDLPS. In summary, GFPT2 is a promising novel antibody demonstrating 85.2% sensitivity and 94.7% specificity.

P1, N=8, Not yet recruiting, Northwestern University

P1, N=22, Active, not recruiting, University Health Network, Toronto | Trial completion date: Sep 2025 --> Nov 2026 | Trial primary completion date: Sep 2025 --> Nov 2026

Adult and embryonic MSCs exhibited overlapping H2AK119ub and H3K4me3/H3K27me3 (bivalent) histone marks, while SS18::SSX-mediated transformation culminated in the widespread loss of H3K27me3 at these genes and their consequent transcription. Collectively, these studies define a rare MSC context, conducive for SS18::SSX-mediated transformation, and demonstrate that SyS tumorigenesis involves the induction and maintenance of an embryonic-like MSC phenotype.

Further, the advancement of CFT8634 as a monotherapy was inhibited by the emergence of cardiac toxicities. Nevertheless, this first study of an orally bioavailable BRD9 degrader recapitulates preclinical pharmacokinetic and pharmacodynamic observations in a clinical trial setting.

P1, N=44, Active, not recruiting, Seattle Children's Hospital | Recruiting --> Active, not recruiting | Trial primary completion date: Jun 2025 --> Jun 2040

This case highlighted the importance of a multidisciplinary approach in diagnosing and managing a rare head and neck SS. Furthermore, this is the first reported case from Pakistan, emphasizing the need for awareness in atypical locations.

TAK-981 synergizes with cytotoxic chemotherapy through increased DNA damage, leading to tumor regression. Targeting the SUMOylation pathway in SS restores cBAF complexes and blocks the SS18::SSX transcriptome, identifying an unappreciated role of SUMOylation in SS and a subsequent therapeutic vulnerability.

P1/2, N=58, Completed, Epizyme, Inc. | Active, not recruiting --> Completed