zoledronic acid

Higher FLOT2 expression in nine HER2 amplified cell lines correlated with a higher T-DM1 IC50 in vitro , and breast cancer patients with high FLOT2 expression had worse survival when receiving either T-DXd (16.2 months (m) vs 18.3 m, p=0.04) or T-DM1 (38.0 m vs 41.3 m, p=0.1) in real-world Caris Life Sciences data. In conclusion, FLOT2 regulates the internalization and cytotoxicity of T-DM1 mediated by Cbl-dependent ubiquitination of HER2. Zoledronic acid disrupts the HER2/FLOT2 interaction, therefore increasing the internalization and cytotoxicity of T-DM1, providing proof of principle that a small molecule inhibitor of the HER2/FLOT2 interaction can enhance the activity of the HER2-targeting ADC.

This first comprehensive FAERS study identifies key drugs associated with ILI, including interferon β-1a, evolocumab, ofatumumab, interferon β-1b, and zoledronic acid. Clinical monitoring for drug-induced ILI is essential to enhance medication safety.

A 59-year-old woman with stage IIIA HR+/HER2- breast cancer underwent modified radical mastectomy in 2016, followed by adjuvant AC-P (doxorubicin hydrochloride 70 mg, cyclophosphamide 800 mg, and paclitaxel liposomes 180 mg) chemotherapy, radiotherapy, and letrozole maintenance...Since palbociclib was not yet covered by insurance, she received an initial chidamide + exemestane therapy, which proved ineffective. Using second-line palbociclib combined with fulvestrant and zoledronic acid therapy, disease stabilization was achieved for up to 12 months...As of September 2023, the patient has remained progression-free for >20 months and experienced only manageable grade 2 diarrhea. This case suggests that sequential CDK4/6 inhibition could help achieve >20 months of progression-free disease control in a patient with bone-only HR+/HER2- MBC after clinical progression during prior palbociclib-based therapy and underscored the need for biomarker-guided strategies in this distinct population.

P1/2, N=30, Not yet recruiting, Assistance Publique Hopitaux De Paris

The patient was treated with vinblastine and prednisolone, along with desmopressin and somatotropin replacement. Zoledronic acid was added for osseous disease...This case highlights an unusual presentation of adult LCH with distal lower-extremity and tarsal bone involvement, as well as hypothalamic-pituitary disease preceding osseous diagnosis by two years. It underscores the importance of considering LCH in adults with unexplained multifocal lytic bone lesions and endocrine dysfunction, and it demonstrates that durable disease control can be achieved with systemic therapy.

For ER+/HER2- early breast cancer, the utility of genomic assays such as Oncotype DX, PAM50, and MammaPrint is discussed, with a focus on chemotherapy selection and the role of CDK4/6 inhibitors, and the role of extended endocrine therapy and adjuvant zoledronic acid. In HER2-positive breast cancer, we examine neoadjuvant therapy with dual HER2 blockade (trastuzumab and pertuzumab), personalized regimens that minimize cardiotoxicity, and the potential of antibody-drug conjugates. For TNBC, the growing role of immunotherapy, dose-dense regimens, and adjuvant capecitabine is reviewed, with a focus on olaparib in BRCA-mutated cases. This review also addresses special populations, including BRCA mutation carriers and premenopausal women, and looks at future trends in systemic therapy, including novel agents, biomarker-driven approaches, and treatment de-escalation strategies.

We established a novel metabolic vulnerability in hormone-responsive malignancies. These findings position ZA as a bifunctional ferroptosis inducer in ER+ breast cancer, offering a promising strategy to overcome endocrine resistance.

CoQ deficiency disrupts oxidative phosphorylation (OXPHOS) and pyrimidine metabolism, causes mitochondrial ROS accumulation, induces mitochondrial antiviral protein (MAVS) oligomerization, and activates the pyrin inflammasome. This mevalonate-CoQ-OXPHOS/pyrimidine metabolism axis serves as a promising target for screening additional immune-metabolic adjuvants, and nanofabrication offers a paradigm for the lymph-targeted in vivo delivery of such adjuvants.

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