Giant Cell Tumor of Bone

P3, N=128, Active, not recruiting, SynOx Therapeutics Limited | Trial primary completion date: Apr 2026 --> Dec 2025

P=N/A, N=140, Completed, The Third Affiliated Hospital of Southern Medical University; The Third Affiliated Hospital of Southern Medical University

The following ten drugs received FDA approval in 2025 - avutometinib (inhibiting MEK1/2 in serous ovarian carcinomas), defactinib (blocking FAK in low grade serous ovarian carcinomas), delgocitinib (antagonizing the JAK family in hand eczema), mirdametinib (inhibiting MEK1/2 in type I neurofibromatosis), remibrutinib (blocking BTK in chronic spontaneous urticaria), rilzabrutinib (antagonizing BTK in chronic immune thrombocytopenia), sunvozertinib (blocking mutant exon 21 insertion EGFR NSCLC), taletrectinib (inhibiting mutant ROS1 in NSCLC), vimseltinib (blocking CSF1R in tenosynovial giant cell tumors), and zongertinib (antagonizing mutant HER2 in NSCLC). This article summarizes the physicochemical properties of all 94 FDA-approved small molecule protein kinase inhibitors including the molecular weight, number of hydrogen bond donors/acceptors, ligand efficiency, lipophilic efficiency, polar surface area, and solubility. A total of 45 of the 94 FDA-approved drugs have a least one Lipinski rule of five violation.

Furthermore, there is an absence of severe toxicities that have arisen with other agents in the TGCT treatment space, specifically liver failure. Vimseltinib is a favorable option for patients with TGCTs and further efforts to determine its place in the sequence of overall management are needed.

Soft tissue recurrence in GCTB may occur independently or following intraosseous recurrence and is frequently observed in high-grade lesions. Although not statistically significant, the findings suggest a possible association between tumor aggressiveness and STR. Histological features remain consistent with osseous lesions, but the diagnostic value of H3F3A expression in STRs warrants fur ther investigation. Importantly, STR represents a distinct recurrence pattern and may be associated with an increased risk of pulmonary metastasis, underscoring the need for vigilant long-term follow-up and systematic surveillance.   Cite this article as: Mirioğlu A, Dalkır KA, Ölke HC, et al. Soft tissue recurrence in giant cell tumor of bone: risk factors and radiological and histopathological features. Acta Orthop Traumatol Turc.,  2025;59(6):470-476.

The results of in vitro-in vivo extrapolation (IVIVE) indicated that coadministration of pexidartinib at a clinically approved dose (400 mg twice daily) with the drugs primarily cleared by UGT1A1, UGT1A6, UGT1A7, UGT1A9, and UGT2B15 would result in a higher risk of DDI. In summary, our results provide useful information for the mechanism underlying pexidartinib-induced hepatotoxicity and clinical safe medication of pexidartinib.

Recognition of gene fusion signatures not only enhances diagnostic precision but also opens avenues for targeted therapy in selected cases. Continued molecular investigation and case accumulation are necessary to validate the biological behavior and therapeutic implications of many of these newly recognized entities.

The H3-3A gene sequencing assay demonstrated a sensitivity of 87.16% and an absolute specificity of 100% among the cases analyzed in the study. Determination of the H3-3A gene mutation by sequencing is a highly sensitive and absolutely specific diagnostic tool for the diagnosis of GCTB and differentiation from its histologic mimics.

There is only one other case that has been documented of a β-hCG-producing GCTBoccurring in the base of the skull with secondary aneurysmal bone cyst-like changes.This appears to be the first reported instance of β-hCG-secreting GCTB in the gnathicbones. This case exemplifies the diagnostic challenges of rare presentations of GCTBand alerts clinicians to the potential misleading presentation of hormone expression.

Aggressive lesions demonstrate reduced lymphocyte infiltration and increased mast cell density, a pattern particularly evident in GCTs of bone. This imbalance may contribute to their aggressive behavior by enabling them to escape host immune regulation.

International, multicentric registries are essential for studying rare diseases like primary spine tumors, enabling robust data collection, improved statistical power, and broader applicability of findings across diverse clinical settings. Ongoing prospective data collection through PTRON will further refine evidence-based care for these rare and challenging conditions.

Higher PD-L1 mRNA expression correlated with accelerated tumor growth in extremity GCTB. These exploratory findings suggest PD-L1 may serve as a potential biomarker of tumor aggressiveness, warranting validation in larger cohorts.