To overcome these hurdles, we developed a bone-targeted, glutathione (GSH)-responsive polymeric nanoparticle (NPALN/Mn-AP) that chelates manganese (Mn) and delivers an ATM inhibitor (AZD0156) and a PRMT5 inhibitor (GSK3326595). By functionalizing this nanoplatform with alendronate (ALN) into NPALN/Mn-AP, we achieve preferential accumulation in bone tumors...In vivo studies demonstrate that NPALN/Mn-AP significantly inhibits OS progression and boosts systemic immune responses. This dual-action, bone-specific nanotherapeutic platform synchronized DNA-repair inhibition and Mn-enhanced immune-stimulation, offering a promising new approach for effective osteosarcoma treatment.

Its function was investigated through small interfering RNA-mediated silencing, lentiviral overexpression, pamidronate treatment, in vitro proliferation, migration, invasion, and apoptosis assays, xenograft models, phosphoproteomic profiling, and Western blot validation. FDPS knockdown was further associated with decreased B-cell lymphoma 2 expression, reduced phosphorylation of Caspase-9 at Ser196, increased cleaved Caspase-3, and reduced phosphorylation of mechanistic target of rapamycin at Ser2448. Collectively, these findings suggest that FDPS contributes to HCC progression and may serve as a candidate biomarker and therapeutic target.

P2, N=30, Not yet recruiting, National Institute of Allergy and Infectious Diseases (NIAID) | Initiation date: Jan 2026 --> Jun 2026

Despite intensive treatment with intravenous hydration and zoledronic acid, neurological deterioration occurred; hence, after 25 days of hospitalization, the patient was discharged for home-based palliative care at the family's request. This case highlights the importance of considering metastatic malignancies, particularly breast cancer, in patients with pancreatitis of unclear etiology and severe hypercalcemia.

Herein, we present a rare case of MTC that caused hypercalcemia via PTHrP production. Although HHM is uncommon in thyroid cancer, the condition can cause severe hypercalcemia requiring prompt diagnosis and treatment. HHM should be considered in patients with thyroid cancer with hypercalcemia, and PTHrP measurement may aid in the diagnosis.

Importantly, the K562 chronic myelogenous leukemia cells that demonstrated an attenuated response to the 3d generation Bcr-Abl tyrosine kinase inhibitor in the medium conditioned by bone marrow-derived fibroblasts, were readily killed by CuZA-cysteine combination. Thus, oxidative burst upon metal reduction in CuZA complexes emerges as a promising method of eradication of tumor cells in the bone microenvironment.

P1/2, N=2, Recruiting, Institute of Hematology & Blood Diseases Hospital, China

However, conventional ex vivo expansion protocols using zoledronic acid (Zol) and IL-2 often lead to terminal differentiation and diminished effector function. In orthotopic tumor models, γδ2 T-Da cells enhanced tumor control, reduced TNBC metastasis, and prolonged survival of GBM-bearing mice. These results suggest that dasatinib improves γδ T cell yield and function, providing a practical and translatable strategy for optimizing γδ T cell-based adoptive therapy, particularly for solid tumors.Trial registration: Trial number: CMUH111-REC3-185.

P1/2, N=12, Active, not recruiting, Dextech Medical AB | Recruiting --> Active, not recruiting

The ATMP was manufactured and validated in a GMP facility and was obtained from leukapheresis stimulated with zoledronic acid and IL-2, afterward depleted of αβ T lymphocytes using the CliniMACS Prodigy...Furthermore, γδ T lymphocytes and NK cells were cytotoxic against myeloid leukemia or neuroblastoma cells. In conclusion, we implemented a novel ATMP to be shortly translated into clinical practice, which may be used in the post-transplant phase as efficacious immunotherapy in neuroblastoma and leukemic pediatric patients.

Simulated treatment of bone-adapted tumors with the bisphosphonate zoledronic acid stabilizes bone density but has limited or highly variable effects on tumor growth. These results suggest that OC inhibition alone may be insufficient to restrain tumor expansion once tumors have adapted to the bone microenvironment. Together, these findings support the hypothesis that tumor adaptation to the bone microenvironment governs dependence on bone-derived growth factors and response to OC-targeted therapy, underscoring the value of mechanistic modeling for elucidating tumor-bone interactions and guiding tumor-type-specific treatment strategies for TIBD.

In this study, we evaluated the impact of human serum on the expansion, phenotype, function, and transcriptomic landscape of Vγ9Vδ2 γδ T cells cultured with zoledronate and cytokines under serum-free versus serum-containing conditions...Furthermore, re-exposure to serum late in culture had minimal influence on γδ T cell functionality. These findings demonstrate the feasibility and advantages of serum-free expansion protocols for Vγ9Vδ2 γδ T cells, offering improved consistency, safety, and therapeutic potential.