Advances in the Repurposing and Blood–Brain Barrier Penetrance of Drugs in Pediatric Brain Tumors

Cancers, Год журнала: 2025, Номер 17(3), С. 439 - 439

Опубликована: Янв. 27, 2025

Central nervous system (CNS) tumors are the leading cause of cancer-related mortality in children, with prognosis remaining dismal for some these malignancies. Though past two decades have seen advancements surgery, radiation, and targeted therapy, major unresolved hurdles continue to undermine therapeutic efficacy. These include challenges suboptimal drug delivery through blood–brain barrier (BBB), marked intra-tumoral molecular heterogeneity, elusive tumor microenvironment. Drug repurposing or re-tasking FDA-approved drugs evidence penetration into CNS, using newer methods intracranial facilitating optimal exposure, has been an area intense research. This could be a valuable tool, as most agents already gone lengthy process development evaluation safety risks pharmacokinetic profile. They can now used tested clinics accelerated different approach. Conclusions: The next-generation strategy should prioritize oncologic non-oncologic that other indication, demonstrated robust preclinical activity against pediatric brain tumors. In combination novel techniques, hold significant promise neurooncology.

Язык: Английский

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The Vital Role Played by Deferiprone in the Transition of Thalassaemia from a Fatal to a Chronic Disease and Challenges in Its Repurposing for Use in Non-Iron-Loaded Diseases

Pharmaceuticals, Год журнала: 2023, Номер 16(7), С. 1016 - 1016

Опубликована: Июль 18, 2023

The iron chelating orphan drug deferiprone (L1), discovered over 40 years ago, has been used daily by patients across the world at high doses (75–100 mg/kg) for more than 30 with no serious toxicity. level of safety and simple, inexpensive synthesis are some many unique properties L1, which played a major role in contribution transition thalassaemia from fatal to chronic disease. Other valuable clinical L1 relation pharmacology metabolism include: oral effectiveness, improved compliance compared prototype therapy subcutaneous deferoxamine; highly effective removal all iron-loaded organs, particularly heart, is target organ toxicity cause mortality thalassaemic patients; an ability achieve negative balance, completely remove excess iron, maintain normal stores rapid absorption stomach clearance body, allowing greater frequency repeated administration overall increased efficacy excretion, dependent on dose also concentration achieved site action; its cross blood–brain barrier treat malignant, neurological, microbial diseases affecting brain. Some differential pharmacological activity among generally shown absorption, distribution, metabolism, elimination, (ADMET) drug. Unique exhibited comparison other drugs include specific protein interactions antioxidant effects, such as transferrin lactoferrin; inhibition copper catalytic production free radicals, ferroptosis, cuproptosis; iron-containing proteins associated different pathological conditions. have attracted interest investigators repurposing use conditions, including cancer, neurodegenerative renal radical pathology, metal intoxication Fe, Cu, Al, Zn, Ga, In, U, Pu, diseases. Similarly, increase prospects wider optimizing therapeutic efforts fields medicine, synergies drugs.

Язык: Английский

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Mebendazole Exerts Anticancer Activity in Ovarian Cancer Cell Lines via Novel Girdin-Mediated AKT/IKKα/β/NF-κB Signaling Axis

Cells, Год журнала: 2025, Номер 14(2), С. 113 - 113

Опубликована: Янв. 14, 2025

Mebendazole (MBZ), a benzimidazole anthelmintic and cytoskeleton-disrupting compound, exhibits antitumor properties; however, its action on ovarian cancer (OC) is not clearly understood. This study evaluates the effect of MBZ OC cell lines OVCAR3 OAW42, focusing proliferation, migration, invasion, stemness. The underlying mechanisms, including cytoskeletal disruption, epithelial–mesenchymal transition (EMT), signaling pathways, were explored. inhibited OAW42 proliferation in dose- time-dependent manner. Additionally, significantly impedes spheroid colony formation, In addition, it reduced actin polymerization down-regulated CSC markers (e.g., CD24, CD44, EpCAM). Moreover, suppressed MMP-9 activity EMT marker as judged by decreased N-Cadherin Vimentin increased E-Cadherin. Furthermore, induced G2/M cycle arrest modulating Cyclin B1, CDC25C, WEE1. Also, triggered apoptosis disrupting mitochondrial membrane potential. Mechanistic studies revealed significant downregulation Girdin, an Akt modulator, along with p-Akt, p-IKKα/β, p-NF-κB, indicating MBZ’s novel mechanism through Girdin-mediated Akt/IKKα/β/NF-κB axis. Thus, targeting presents promising repurposed therapeutic strategy to inhibit metastasis cancer.

Язык: Английский

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Individualized therapeutic approaches for relapsed and refractory pediatric ependymomas: a single institution experience

Journal of Neuro-Oncology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 16, 2025

Abstract Purpose This retrospective study aims to show a real-life single-center experience with clinical management of relapsed pediatric ependymomas using results from comprehensive molecular profiling. Methods Eight were tested by whole exome sequencing, RNA phosphoproteomic arrays, array comparative genome hybridization, and immunohistochemistry staining for PD-L1 expression treated an individualized approach implementing targeted inhibitors, immunotherapy, antiangiogenic metronomic treatment, or other agents. Treatment efficacy was evaluated progression-free survival (PFS), overall (OS), after relapse (SAR), PFS ratios. Results Genomic analyses did not reveal any therapeutically actionable alterations. Surgery remained the cornerstone patient supplemented adjuvant radiotherapy. Empiric agents chosen quite frequently, often involving drug repurposing. In six patients, prolonged seen because MEMMAT, empiric is reflected in ratio ≥ 1. The 5-year OS 88%, 10-year 73%, 2-year SAR 66%. Conclusion We demonstrated feasibility good safety profile. Promising effect immunotherapy on ZFTA-positive ependymomas. However, further research required establish most effective achieving sustained remission these patients.

Язык: Английский

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Prevalence and Radiographic Characteristics of Cerebral Infarction after Surgery in Patients with Glioma: A Retrospective Study

Annali Italiani di Chirurgia, Год журнала: 2024, Номер 95(3), С. 338 - 346

Опубликована: Июнь 20, 2024

Язык: Английский

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