Emerging therapeutics in the management of tenosynovial giant cell tumor (TGCT).

Introduction: Tenosynovial giant cell tumors (TGCTs) are locally aggressive mesenchymal neoplasms that often occur in younger patients and cause long-term disability. Surgical management remains the standard of care, but with high risks of surgical morbidity, systemic treatment options are important to consider, particularly in diffuse disease. Improved understanding of the molecular pathogenesis of TGCTs has led to exciting developments in this arena.

Areas covered: This review aims to provide historical context for systemic treatments for patients with TGCTs with a focus on the diffuse subtype (DT-TGCT) while exploring the more recently available treatments in depth. Current literature on TGCTs and therapy was reviewed and summarized by a comprehensive search of MEDLINE (1/1/1989-11/30/2024). We also suggest directions for future investigation in the systemic treatment space for TGCT with a goal to alleviate symptoms and improve quality of life while minimizing treatment-related toxicity.

Expert opinion: Advances in the understanding of the molecular pathogenesis of TGCT has led to systemic therapies targeting the CSF1 receptor (CSF1R), including the first FDA approval in this space of pexidartinib. These developments provide the foundation for further investigation into additional treatments, optimal sequencing, and duration of therapies for patients with symptoms and reduced functionality secondary to TGCT.