Current therapies, such as bisphosphonates and denosumab, offer limited survival benefits and carry significant safety risks, highlighting the need for novel agents that effectively inhibit osteolytic progression...rLGR4-ECD effectively inhibits RANKL-induced osteoclastogenesis and reduces bone metastasis burden through specific suppression of osteoclast activity, leading to improved survival in a preclinical model. Its excellent efficacy and manufacturability support its potential as a novel therapeutic agent for bone metastatic disease.

P4, N=102, Active, not recruiting, Amgen | Recruiting --> Active, not recruiting

These findings demonstrate MHP1-AcN as a novel LGR4 antagonist that inhibits RSPO3-LGR4-Wnt signaling, tumor growth, and metastatic potential in lung adenocarcinoma, highlighting its potential as a therapeutic agent targeting this pathway.

Moreover, DNB/BMP-2 significantly improved torsional stiffness and maximum compressive force versus either treatment alone (all P < 0.05). The findings demonstrate that systemic DNB combined with local BMP-2 rapidly promotes femoral metaphyseal bone regeneration in osteoporotic rats.

Pharmacological inhibition of CARM1 (TP-064) effectively suppressed osteoclastogenesis and bone metastasis in denosumab-resistant models. These findings revealed a targetable resistance mechanism and provided a clinically actionable strategy to overcome microenvironment-driven metastasis through dual targeting of tumor and bone niches.

P4, N=54, Completed, Tuen Mun Hospital | Recruiting --> Completed

Giant cell tumor of bone (GCTB) is an intermediate bone neoplasm defined by recurrent H3F3A mutations and limited systemic treatment options beyond denosumab...Functionally, 3D culture generally reduced sensitivity to many agents while preserving compound-dependent vulnerabilities. These results establish culture dimensionality as a key determinant of therapeutic susceptibility in GCTB PDCs and support incorporating proteome-informed 3D models into translational pipelines to prioritize clinically relevant drug candidates and biomarkers.

P4, N=45, Completed, University of Alabama at Birmingham | Active, not recruiting --> Completed

This case is discussed within the context of a comprehensive narrative review highlighting the distinct biological behavior of calvarial GCTB compared to skull-base lesions, the critical importance of achieving gross total resection, and the emerging role of molecular diagnosis (H3F3A G34W mutation) and adjuvant therapies including denosumab. Calvarial GCTB offers superior surgical accessibility and prognosis compared to skull-base counterparts, with appropriately aggressive resection typically achieving cure without need for radiotherapy, thereby avoiding the well-documented risk of radiation-induced malignant transformation.

P2, N=50, Not yet recruiting, Tongji Hospital

Our results support the feasibility of neoadjuvant systemic therapy in resectable NSCLC and explore the novel combination of nivolumab with denosumab. CD8 T-cell infiltration correlates with pathological response, warranting ongoing translational research to better understand patient selection for such novel combinations.