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DRUG:

zoledronic acid

i
Other names: CGP 42446, ZOL 446, CGP 42446A, AK-156
Company:
Generic mfg.
Drug class:
Bone resorption factor inhibitor, Osteoclast inhibitor
2d
Zoledronic Acid Inhibits Lipopolysaccharide-Induced Osteoclastogenesis by Suppressing Macrophage NLRP3-Mediated Autophagy Pathway. (PubMed, Immun Inflamm Dis)
ZOL has a certain immunomodulatory effect that exhibits anti-inflammatory properties at lower concentrations, which can weaken LPS-induced OCs differentiation and function, and NLRP3-mediated autophagy pathway may participate in this process.
Journal
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TNFA (Tumor Necrosis Factor-Alpha) • NLRP3 (NLR Family Pyrin Domain Containing 3) • ATG7 (Autophagy Related 7) • BECN1 (Beclin 1)
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zoledronic acid
2d
Journal
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TNFA (Tumor Necrosis Factor-Alpha) • IL1B (Interleukin 1, beta) • CRP (C-reactive protein)
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zoledronic acid
18d
Remission of longstanding metastatic paraganglioma in a patient after use of zoledronic acid. (PubMed, BMJ Case Rep)
Stability of disease was further demonstrated by CT over several years. The patient continues on surveillance.
Journal • Metastases
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SSTR (Somatostatin Receptor)
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zoledronic acid
20d
New P4 trial
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dexamethasone • zoledronic acid
21d
SLFN12 Expression Significantly Effects the Response to Chemotherapy Drugs in Triple-Negative Breast Cancer. (PubMed, Cancers (Basel))
These results suggest that SLFN12 overexpression significantly affects the expressions of genes driving phenotypic changes in response to chemotherapy and influences additional SLFN family members following IFN-α2 treatment. This may contribute to improving the survival of patients with SLFN12 overexpression. Additionally, patient SLFN12 levels can be used as a factor when pursuing personalized chemotherapy treatments.
Journal
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IFNA1 (Interferon Alpha 1) • GJB3 (Gap Junction Protein Beta 3)
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carboplatin • paclitaxel • zoledronic acid
23d
Fatty acid composition and anti-cancer activity of essential oil from Tenebrio molitor larvae in combination with zoledronic acid on prostate cancer. (PubMed, Heliyon)
In conclusion, EOTM exhibits strong anticancer properties by inducing apoptosis in prostate cancer cells and demonstrates synergistic potential when combined with zoledronic acid. These findings warrant further investigation of EOTM as a natural and effective cancer treatment option.
Journal • Combination therapy • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • BAX (BCL2-associated X protein)
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BCL2 expression • BAX expression
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zoledronic acid
28d
Romosozumab As an Adjunct to Physiologic Estrogen Replacement in Functional Hypothalamic Amenorrhea (clinicaltrials.gov)
P3, N=114, Not yet recruiting, Massachusetts General Hospital | Initiation date: Oct 2024 --> Jan 2025
Trial initiation date
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zoledronic acid
29d
Denosumab to Prevent High-Turnover Bone Loss After Bariatric Surgery (clinicaltrials.gov)
P4, N=36, Completed, Massachusetts General Hospital | Active, not recruiting --> Completed
Trial completion • Surgery • Bariatric surgery
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Prolia (denosumab) • zoledronic acid
30d
Elotuzumab-mediated ADCC with Th1-like Vγ9Vδ2 T cells to disrupt myeloma-osteoclast interaction. (PubMed, Cancer Sci)
Human Th1-like Vγ9Vδ2 (γδ) T cells, important effectors against tumors, can be expanded and activated ex vivo by the aminobisphosphonate zoledronic acid in combination with IL-2. These results demonstrate that SLAMF7 is highly expressed in both MM cells and OCs, and that the ex vivo-expanded γδ T cells can exert ELO-mediated ADCC against SLAMF7-expressing MM cells and OCs besides their direct cytotoxic activity. Further study is warranted for the innovative utilization of γδ T cells.
Journal
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IL2 (Interleukin 2) • CSF1 (Colony stimulating factor 1) • SLAMF7 (SLAM Family Member 7)
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Empliciti (elotuzumab) • zoledronic acid
1m
Alpha/Beta CD19+ Depleted Haploidentical Transplantation + Zometa for Pediatric Hematologic Malignancies and Solid Tumors (clinicaltrials.gov)
P1, N=22, Recruiting, University of Wisconsin, Madison | Suspended --> Recruiting | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025
Enrollment open • Trial completion date • Trial primary completion date
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melphalan • zoledronic acid
2ms
Multifunctional ICG-SB@Lip-ZA Nanosystem Focuses on Remodeling the Inflammatory-Immunosuppressive Microenvironment After Photothermal Therapy to Potentiate Cancer Photothermal Immunotherapy. (PubMed, Adv Healthc Mater)
Indocyanine green (ICG) as a photothermal-transducer ablated tumor cells, zoledronic acid (ZA) depletes TAMs recruited by the inflammatory tumor microenvironment (mostly M2-like phenotype), SB-505124 affects CAFs proliferation in the tumor microenvironment (TME) by inhibiting the transforming growth factor-β (TGF-β) pathway, thereby removing physical barriers to T cell infiltration. In a breast cancer model, these immunomodulatory nanoliposomes markedly decrease the population of M2-like TAMs in the TME, eliminate physical barriers hindering T cell infiltration, reshape the inflammatory immune-suppressive tumor microenvironment, eventually leading to a rate of tumor eradication of 94%. This multifunctional ICG-SB@Lip-ZA nanosystem (including photothermal conversion, TAM depletion, and TGF-β pathway blockade) offers a promising strategy for mitigating the deteriorating tumor microenvironment following PTT and presents a more efficient approach for clinical photothermal-immune combination therapy.
Journal
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TGFB1 (Transforming Growth Factor Beta 1)
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zoledronic acid
2ms
An Impressive Response to Zoldronic Acid Treatment for Chronic Recurrent Multifocal Osteomyelitis: A Case Report. (PubMed, J Investig Med High Impact Case Rep)
Data on the use of zoledronic acid (ZA) in juvenile CRMO are scarce...The patient's condition stayed stable while taking naproxen (20 mg/kg/day) and methotrexate (10 mg/week) for 1.5 years until he experienced right elbow pain, swelling, no overlying skin erythema, and a restricted range of motion...Non-steroidal anti-inflammatory drugs and methotrexate were initially effective in treating our patient's condition, but a recurrence necessitated treatment modification. To the best of our knowledge, this case is the first documented instance of the use of ZA in CRMO in Iraq and Arab nations.
Journal
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CRP (C-reactive protein)
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methotrexate • zoledronic acid
2ms
DiTuSarc: Treatment with Dinutuximab Beta, Zoledronic Acid and Low-dose Interleukin (IL-2) in Patients with Leiomyosarcoma (clinicaltrials.gov)
P2, N=10, Active, not recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Recruiting --> Active, not recruiting | Trial completion date: Jul 2024 --> Jan 2025
Enrollment closed • Trial completion date • Metastases
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zoledronic acid • Qarziba (dinutuximab beta)
2ms
Trial suspension
|
melphalan • zoledronic acid
2ms
Local Bisphosphonate Effect on Recurrence Rate in Extremity Giant Cell Tumor of Bone (clinicaltrials.gov)
P3, N=120, Recruiting, St. Louis University | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2025 --> Jan 2026
Trial completion date • Trial primary completion date
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zoledronic acid
3ms
New P1/2 trial
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zoledronic acid
3ms
STAT6/LINC01637 axis regulates tumor growth via autophagy and pharmacological targeting STAT6 as a novel strategy for uveal melanoma. (PubMed, Cell Death Dis)
Finally, molecular docking indicated that STAT6 is a target of Zoledronic Acid, which can delay UM tumorigenicity by inhibiting STAT6 expression. Taken together, our results indicate that the STAT6/LINC01637 axis promotes UM progression via autophagy and may serve as a potential therapeutic target for UM.
Journal
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STAT6 (Signal transducer and activator of transcription 6)
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zoledronic acid
3ms
The Potential of Enamel Matrix Derivative in Countering Bisphosphonate-Induced Effects in Osteoblasts. (PubMed, Life (Basel))
While the suppressive effect of zoledronate (Zol) on cell viability and migration was observed, the addition of EMD significantly mitigated this effect and enhanced cell viability and migration...This finding suggests that EMD could mitigate the effects of BPs, resulting in the recovery of cell survival, migration, and gene and protein expression. However, the behavior of the osteoblasts was not fully restored, and further studies are necessary to confirm their effects at the cellular level and to assess their clinical usefulness in vivo for the prevention and treatment of MRONJ.
Journal
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CSF1 (Colony stimulating factor 1) • ALPL (Alkaline Phosphatase)
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zoledronic acid
3ms
Drug induced lupus associated with Trastuzumab emtansine in a patient with metastatic breast cancer. (PubMed, J Oncol Pharm Pract)
Drug-induced lupus is a clinical syndrome that shares similar features with systemic lupus erythematosus (SLE). The majority of patients present with symptoms such as arthralgia and myalgia. Hydralazine and procainamide are high-risk drugs for drug-induced lupus. Symptoms usually develop after months or years of use, but may also develop suddenly. Our patient also received TDM-1 treatment for 18 months. We present a case of TDM-1-associated drug-induced lupus in a patient with metastatic breast cancer. This is the first case of TDM-1-related drug-induced lupus reported in the literature.
Journal • Metastases
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 positive
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docetaxel • Perjeta (pertuzumab) • Kadcyla (ado-trastuzumab emtansine) • hydroxychloroquine • zoledronic acid
3ms
TOPaZ: Treatment of Osteogenesis Imperfecta With Parathyroid Hormone and Zoledronic Acid (clinicaltrials.gov)
P4, N=350, Active, not recruiting, University of Edinburgh | Recruiting --> Active, not recruiting | Trial completion date: Apr 2023 --> Jul 2025 | Trial primary completion date: Dec 2022 --> Feb 2025
Enrollment closed • Trial completion date • Trial primary completion date
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zoledronic acid
3ms
Observation and comparison of the direct efficacy of denosumab and zoledronic acid on bone metastases (ChiCTR2400088456)
P=N/A, N=100, Completed, The 2nd Affiliated Hospital of Chongqing Medical University; The 2nd Affiliated Hospital of Chongqing Medical University
New trial
|
Prolia (denosumab) • zoledronic acid
3ms
A prospective randomized controlled study of Denosumab and zoledronic acid in the treatment of female osteoporotic fractures (ChiCTR2400083430)
P=N/A, N=300, Recruiting, Shanghai Jiaotong University School of Medicine Affiliated Ruijin Hospital; Shanghai Jiaotong University School of Medicine Affiliated Ruijin Hospital | Not yet recruiting --> Recruiting
Enrollment open
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Prolia (denosumab) • zoledronic acid
3ms
Dual-pore protocells with multitasking capacities for simultaneous delivery of therapeutic enzymes and drugs in macrophage depletion therapy. (PubMed, Biomater Sci)
This nanodevice is composed of a dual-pore mesoporous silica core with the capacity to house small cytotoxic drugs, such as doxorubicin or zoledronic acid, and large macromolecules, such as glucose oxidase. Once there, the nanoassemblies also exhibited excellent capacity to induce potent macrophage depletion. This strategy can be directly adapted for the treatment of different malignancies due to the modular nature of the nanoplatform, which can be loaded with different therapeutic agent combinations and pave the way for the development of personalized nanomedicines for diverse types of tumors.
Journal
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CAT (Catalase)
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doxorubicin hydrochloride • zoledronic acid
3ms
Hyaluronic acid-covered ferric ion-rich nanobullets with high zoledronic acid payload for breast tumor-targeted chemo/chemodynamic therapy. (PubMed, Int J Biol Macromol)
Importantly, the in vivo studies and ki67 and GPX4 staining of tumor sections demonstrated that the ZA@HMNs efficiently accumulated in 4T1 tumors to hinder tumor growth via ZA chemotherapy combined with OH-mediated ferroptosis. This work presents a practicable strategy to fabricate ZA@HMNs for breast tumor-targeted chemo/chemodynamic therapy with potential clinical translation.
Journal
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GPX4 (Glutathione Peroxidase 4)
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zoledronic acid
4ms
The Functional Interaction of KATP and BK Channels with Aquaporin-4 in the U87 Glioblastoma Cell. (PubMed, Biomedicines)
The KATP channels are effective in the M1 AQP4-tetramer and M23 AQP4-OAP cells. Zoledronic acid can be effective in targeting pathogenic M1 AQP4-tetramer cell phenotypes inhibiting KATP channels and inducing early apoptosis.
Journal
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ABCC9 (ATP Binding Cassette Subfamily C Member 9) • AQP4 (Aquaporin 4) • MED23 (Mediator Complex Subunit 23)
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zoledronic acid
4ms
Surface Engineered Osteoblast-Extracellular Vesicles Serve as an Efficient Carrier for Drug and Small RNA to Actively Target Osteosarcoma. (PubMed, ACS Biomater Sci Eng)
This study aims to utilize EVs for OS management by co-delivering Hdac1 siRNA and zoledronic acid (zol)...Furthermore, EVs were used as the carrier for co-loading drug (zol) and small RNA (Hdac-1). This approach of using surface engineered EVs as carriers for cargo loading and delivery can be a promising strategy for osteosarcoma management.
Journal
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HDAC1 (Histone Deacetylase 1)
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zoledronic acid
4ms
The role of protein prenylation inhibition through targeting FPPS by zoledronic acid in the prevention of renal fibrosis in rats. (PubMed, Sci Rep)
In conclusion, ZA preserved renal function and prevented renal fibrosis in a rat model. These were achieved through targeting protein prenylation mainly by inhibiting FPPS.
Preclinical • Journal
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IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CASP3 (Caspase 3) • TGFB1 (Transforming Growth Factor Beta 1) • CAT (Catalase) • FDPS (Farnesyl Diphosphate Synthase)
|
zoledronic acid
4ms
TFEB controls sensitivity to chemotherapy and immuno-killing in non-small cell lung cancer. (PubMed, J Exp Clin Cancer Res)
This work suggests that TFEB is a gatekeeper of the sensitivity to chemotherapy and immuno-killing in NSCLC, and that the TFEBlowABCA1lowABCC1high phenotype can be predictive of poor response to chemotherapy and immunotherapy. By reshaping both cancer metabolism and tumor immune-microenvironment, zoledronic acid can re-sensitize TFEBlow NSCLCs, highly resistant to chemo- and immunotherapy.
Journal • IO biomarker
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CD8 (cluster of differentiation 8) • ABCC1 (ATP Binding Cassette Subfamily C Member 1) • CD34 (CD34 molecule) • MAPK1 (Mitogen-activated protein kinase 1) • TFEB (Transcription Factor EB 2) • ABCA1 (ATP Binding Cassette Subfamily A Member 1) • MAPK3 (Mitogen-Activated Protein Kinase 3)
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cisplatin • zoledronic acid
5ms
New P3 trial
|
zoledronic acid
5ms
BonEnza: Luteinizing Hormone-releasing Hormone Analogue and Enzalutamide +/- Zoledronic Acid in Prostate Cancer Patients (clinicaltrials.gov)
P2, N=126, Completed, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia | Recruiting --> Completed
Trial completion • Metastases
|
Xtandi (enzalutamide) • zoledronic acid
5ms
Palbociclib and Fulvestrant Combined Regimen Induced Prolonged Bone Metastasis Control of Stage IV HR+/HER2- Breast Cancer: A Case Report. (PubMed, Radiol Case Rep)
The patient was started on therapeutic doses of letrozole and zoledronic acid in conjunction with adjuvant radiotherapy...A decision was made to switch letrozole for tamoxifen which resulted in disease stability...Palbociclib and fulvestrant were started accordingly, yielding a remarkable metabolic response of all bone metastatic lesions (stable disease) after three months of the regimen initiation. The aforementioned stable disease status continued for approximately three years up to this point.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • CDK4 (Cyclin-dependent kinase 4)
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Ibrance (palbociclib) • tamoxifen • fulvestrant • letrozole • zoledronic acid
5ms
Exploring the Clinical Impact of RANK Pathway Inhibition in Advanced Breast Cancer: Insights From a Retrospective Study on CDK4/6 Inhibitors and Antiresorptive Therapy. (PubMed, Cureus)
This study highlights the potential clinical relevance of the RANK pathway in BC treatment, and our findings suggest that denosumab may offer significant benefits in terms of PFS and OS for certain subgroups, particularly those with HER2 scores of 1, patients under 60, and those with endocrine-resistant BC. In conclusion, considering that RANK pathway status may be a predictive biomarker for CDK4/6i treatment and may cause treatment resistance, our results demonstrate the clinical relevance of the combination of CDK4/6i + ET with RANKL inhibition.
Retrospective data • Journal • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • TNFRSF11A (TNF Receptor Superfamily Member 11a)
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Ibrance (palbociclib) • Kisqali (ribociclib) • Prolia (denosumab) • zoledronic acid
5ms
REaCT-HOLD BMA: Comparing Continuation or De-escalation of Bone Modifying Agents (BMA) in Patients Treated for Over 2 Years for Bone Metastases From Either Breast or Castration-resistant Prostate Cancer (clinicaltrials.gov)
P4, N=240, Active, not recruiting, Ottawa Hospital Research Institute | Recruiting --> Active, not recruiting | Trial completion date: Nov 2025 --> Jun 2026 | Trial primary completion date: Nov 2024 --> Jun 2025
Enrollment closed • Trial completion date • Trial primary completion date
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Prolia (denosumab) • zoledronic acid • pamidronate disodium
5ms
Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
zoledronic acid
5ms
New P1 trial • Combination therapy • Metastases
|
Keytruda (pembrolizumab) • Prolia (denosumab) • zoledronic acid • ETC-159
5ms
Pembrolizumab with external radiation therapy effectively controlled TMB-high unresectable recurrent parathyroid cancer: a case report with review of literature. (PubMed)
He successfully achieved evocalcet and zoledronate withdrawal, and the PTH level improvement was continuously observed for 8 months at present, with only grade 2 subclinical hypothyroidism. A combination of PEM and RT is a promising treatment of unresectable TMB-high PC. Recent evidence on the immunomodulatory effect of RT provides the rationale for the combination of RT and PEM.
Journal • Review • Tumor mutational burden • PD(L)-1 Biomarker
|
FoundationOne® CDx
|
Keytruda (pembrolizumab) • zoledronic acid
6ms
Trial completion • Real-world evidence • Real-world
|
zoledronic acid
6ms
Survival outcomes of Zo-NAnTAx: a five-year analysis of zoledronic acid added to a neoadjuvant regimen for HER2-positive breast cancer. (PubMed, Ann Transl Med)
Adult women with HER2-positive breast cancer amendable to curative surgery who consented to the study received four cycles of ZA at 4 mg + doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 followed by four cycles of ZA at 4 mg + docetaxel 100 mg/m2 + trastuzumab 6 mg/kg (8 mg/kg as a loading dose), all in a 21 days-cycle, totalizing 8 cycles before surgery. ZA plus neoadjuvant therapy in HER2-positive breast cancer shows provoking survival outcomes. Clinical and pre-clinical investigation with dual anti-HER2 blockage is warranted.
Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
Herceptin (trastuzumab) • docetaxel • doxorubicin hydrochloride • cyclophosphamide • zoledronic acid
7ms
Payload-delivering engineered γδ T cells display enhanced cytotoxicity, persistence, and efficacy in preclinical models of osteosarcoma. (PubMed, Sci Transl Med)
Moreover, stIL15-OPS-γδ T cells were efficacious against patient-derived osteosarcomas in animal models and in vitro, where efficacy could be boosted with the addition of zoledronic acid. Together, the data identify stIL15-OPS-γδ T cells as a candidate allogeneic cell therapy platform combining direct cytolysis with bystander activation to promote tumor control.
Preclinical • Journal
|
IL15 (Interleukin 15)
|
zoledronic acid
7ms
Antibody-Drug Conjugate Made of Zoledronic Acid and the Anti-CD30 Brentuximab-Vedotin Exert Anti-Lymphoma and Immunostimulating Effects. (PubMed, Cells)
Eventually, Bre-Ved-ZA ADC, in contrast with the native antibody, can trigger the proliferation and activation of cytolytic activity of effector-memory Vδ2 T-lymphocytes against HL-cell lines. These findings may support the potential use of this ADC in the management of r/r HL.
Journal
|
LAMP1 (Lysosomal Associated Membrane Protein 1)
|
Adcetris (brentuximab vedotin) • zoledronic acid
7ms
Efficacy of Zoledronic Acid to Prevent Bone Loss Following Denosumab Discontinuation (clinicaltrials.gov)
P=N/A, N=20, Active, not recruiting, University of Calgary | Recruiting --> Active, not recruiting
Enrollment closed
|
Prolia (denosumab) • zoledronic acid
8ms
A Unique Case of Oncocytic Thyroid Cancer With an NBN Gene Pathogenic Variant (ENDO 2024)
Due to disease progression, lenvatinib was initiated...Zoledronic acid was initiated for the treatment of the skeletal metastases, and palliative external beam radiation (2000 cGy in 5 fractions) was administered to the sternal lesion to alleviate the bone pain... The NBN gene encodes for the protein nibrin, a member of the MRE11/RAD50 complex that is involved in DNA repair. PVs in NBN are commonly identified in non-thyroidal malignancies such as breast and lung carcinomas. While NBN PVs are rarely reported in DTCs, as per our knowledge, this is the first described case of OTC with a PV in NBN as the molecular driver, manifesting with an aggressive disease course.
Clinical
|
NRAS (Neuroblastoma RAS viral oncogene homolog) • RAD50 (RAD50 Double Strand Break Repair Protein) • NKX2-1 (NK2 Homeobox 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • DAXX (Death-domain associated protein) • PAX8 (Paired box 8) • TG (Thyroglobulin)
|
TTF1 negative
|
Oncomine™ Comprehensive Assay v3M
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Lenvima (lenvatinib) • zoledronic acid