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Emerging therapeutic strategies in glioblastsoma: drug repurposing, mechanisms of resistance, precision medicine, and technological innovations.

Glioblastoma (GBM) is an aggressive Grade IV brain tumor with a poor prognosis. It results from genetic mutations, epigenetic changes, and factors within the tumor microenvironment (TME). Traditional treatments like surgery, radiotherapy, and chemotherapy provide limited survival benefits due to the tumor's heterogeneity and resistance mechanisms. This review examines novel approaches for treating GBM, focusing on repurposing existing medications such as antipsychotics, antidepressants, and statins for their potential anti-GBM effects. Advances in molecular profiling, including next-generation

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… Mebendazole Mebendazole, an FDA-approved anthelmintic drug with microtubule-inhibiting properties, holds promise for GBM treatment. Its effectiveness in crossing the BBB depends on its crystalline polymorph form, with polymorphs B and C being more effective for CNS delivery. … Mebendazole is generally safe, although high concentrations may cause bone marrow and liver toxicity. It is thought to inhibit protein kinase activity, and further investigation is needed to understand its role in cell death and microtubule destabilization [ 126 ]. …

Rethinking corticosteroids use in oncology.

Corticosteroids (CSs), widely used in oncology for their anti-inflammatory and immunosuppressive properties, help manage cancer-related symptoms and side effects. However, their long-term use may negatively affect patient survival and exacerbate tumor progression. Elevated glucose and glutamine metabolism, disruption of vitamin D levels, and alterations in the microbiome are some of the key factors contributing to these adverse outcomes. Approaches such as ketogenic diets, fasting, sartans, and vitamin D supplementation have shown promise in providing similar benefits to CSs while mitigating t

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… Mebendazole, for instance, inhibits glycolysis and glutaminolysis (specifically Glutaminase C for glutaminolysis) ( Mukherjee et al., 2023 ), while 6-diazo-5-oxo-L-norleucine (DON), a pan-glutaminase inhibitor, exhibits potent antitumor activity ( Olsen et al., 2015 ) by simultaneously inhibits glycolysis … Ketogenic diet as a metabolic vehicle for enhancing the therapeutic efficacy of mebendazole and devimistat in preclinical pediatric glioma. Muñoz A., Grant W. B. (2022). Vitamin D and cancer: an historical overview of the epidemiology and mechanisms. …

Strongyloides stercoralis hyperinfection after corticosteroid therapy: a report of two cases.

Two cases of Strongyloides stercoralis hyperinfection are described. Both patients were expatriates from the Indian subcontinent, and reported the use of corticosteroids. The first patient presented with severe pulmonary disease that necessitated respiratory support, followed by acute abdomen and intestinal obstruction and he succumbed to these diseases. The second patient also presented with acute pulmonary disease, which responded to antihelmintic treatment and supportive care; however, he died later due to his primary disease. The clinical features of S stercoralis hyperinfection are nonspe

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… Serologic testing is now widely available and is sensitive but not specific. 2 A single test does not reliably distinguish past from current infection. 2 14 Albendazole, mebendazole, thiabendazole, and ivermectin have been shown to be effective for S stercoralis infection. 15 16 Recently, there has been …

Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells.

Colorectal cancer (CRC) represents the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide. The modern concept of cancer biology indicates that cancer is formed of a small population of cells called cancer stem cells (CSCs), which present both pluripotency and self-renewal properties. These cells are considered responsible for the progression of the disease, recurrence and tumor resistance. Interestingly, some cell signaling pathways participate in CRC survival, proliferation, and self-renewal properties, and most of them are dysregulated in CSCs, includ

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… Mebendazole, an anthelmintic agent, has also been identified as a selective TNIK inhibitor [ 116 ]. … The combination of mebendazole and sulindac, a non‐steroidal anti‐inflammatory agent, reduced tumor initiation in CRC in a preclinical model [ 117 ]. 36‐077 36‐077, an inhibitor of phosphatidylinositol 3‐kinase catalytic subunit type 3 (PIK3C3), was synthetized by Kumar et al. [ 118 ] as a potent autophagy …

Drug Repurposing in Veterinary Oncology: Myth or Reality?

Drug repurposing, that is, the identification of new therapeutic indications for existing medications, has been shown to be a cost-effective and time-efficient alternative to de novo drug development. This review provides a comprehensive overview of repurposed drugs in veterinary oncology, describing their mechanisms of action, current evidence of clinical benefit, and translational relevance. The therapeutic agents discussed include non-steroidal anti-inflammatory drugs (e.g., piroxicam), metabolic modulators (e.g., metformin), anti-parasitic drugs (e.g., fenbendazole), immunomodulators (e.g.

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… hallmarks, including anti-inflammatory and immunomodulatory effects (e.g., piroxicam, thalidomide) [ 9 , 10 ], metabolic interference (e.g., metformin, disulfiram) [ 11 , 12 ], angiogenesis inhibition (e.g., statins, propranolol) [ 13 , 14 ], apoptosis induction, and cell cycle arrest (e.g., fenbendazole, mebendazole … Phase 1 study of mebendazole therapy for refractory/progressive or recurrent pediatric brain tumors. Neurooncol. Pract. 2025 doi: 10.1093/nop/npaf060. in press . 27. Gao P., Dang C.V., Watson J. Unexpected antitumorigenic effect of fenbendazole when combined with supplementary vitamins. J. Am. …

Unlocking hidden potential: advancements, approaches, and obstacles in repurposing drugs for cancer therapy.

High rates of failure, exorbitant costs, and the sluggish pace of new drug discovery and development have led to a growing interest in repurposing "old" drugs to treat both common and rare diseases, particularly cancer. Cancer, a complex and heterogeneous disease, often necessitates a combination of different treatment modalities to achieve optimal outcomes. The intrinsic polygenicity of cancer, intricate biological signalling networks, and feedback loops make the inhibition of a single target frequently insufficient for achieving the desired therapeutic impact. As a result, addressing these c

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… NCT00295035 Genistein | Menopause, osteoporosis, obesity [ 152 ] | hTERT, Wnt/β-catenin, cAMP/PKA | Prostate cancer NCT00584532 Bladder cancer NCT00118040 [ 153 ] Berberine | Bacterial diarrhoea [ 90 ] | Ephrin-B2, MMP-2/MMP-9, EMT, miR-101, VEGF | Colorectal adenoma [ 154 ] NCT02226185 NCT03281096 Mebendazole … Nygren P Larsson R Drug repositioning from bench to bedside: tumour remission by the antihelmintic drug mebendazole in refractory metastatic colon cancer Acta Oncol 2014 53 427 8 24160353 10.3109/0284186X.2013.844359 156. …

Understanding DMG: current treatment options and prospective solutions using nanoparticles.

Diffuse Midline Gliomas (DMGs), which include the subset formerly known as Diffuse Intrinsic Pontine Glioma (DIPG), are associated with an extremely poor prognosis and a five-year survival rate below 2-3%. The devastating prognosis stems from an inherently invasive nature, a deep, anatomically restricted location, rapid cellular drug efflux mediated by transporters such as P-glycoprotein (ABCB1) and breast cancer resistance protein (BCRP/ABCG2), and an immunologically "cold" microenvironment. Coupled with limited Blood-Brain Barrier (BBB) permeability, these biological factors render conventio

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… NCT02644291 I PO Pediatrics Targeted small-molecule therapy Pediatric gliomas Intra-arterial delivery of Melphalan Hydrocholoride NCT01688401 I/II IV Pediatrics VEGF Recurrent/refractory CNS tumors Mebendazole + vincristine, carboplatin, and temozolomide NCT01837862 I/II PO Pediatrics Kinase pathway … | NCT02644291 | I | PO | Pediatrics | Targeted small-molecule therapy | Pediatric gliomas Intra-arterial delivery of Melphalan Hydrocholoride | NCT01688401 | I/II | IV | Pediatrics | VEGF | Recurrent/refractory CNS tumors Mebendazole + vincristine, carboplatin, and temozolomide | NCT01837862 | I/II …

Достижения в области диагностических средств и терапевтических подходов к глиомамам: всеобъемлющий обзор.

Глиомы, широко распространенная категория первичных злокачественных опухолей мозга, создают огромные клинические проблемы из-за их инвазивного характера и ограниченных возможностей лечения. Нынешний терапевтический ландшафт для глиомов сдерживается ".one-Эта парадигма подходит для всех, что существенно ограничивает эффективность лечения. Несмотря на осуществление стратегий мультимодального лечения, показатели выживаемости по-прежнему вызывают разочарование. Традиционный подход к лечению, предусматривающий хирургическое пересечение, излучение и химиотерапию, сталкивается с серьезными ограничени

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… . | USA | 2020–2022 | [ 31 ] Mebendazole (MBZ) combination therapy with lomustine (CCNU) or temozolomide (TMZ) in recurrent glioblastomas | Phase II Randomized open-label trial CTRI/2018/01/011542 | CCNU+MBZ (mebendazole) arm: CCNU: 110 mg/m 2 every 6 weeks; MBZ: 800 mg thrice daily. … . | 44 patients randomized in each arm | The addition of mebendazole (MBZ) to temozolomide (TMZ) or lomustine (CCNU) did not attain the predefined benchmark of a 55% 9-month overall survival (OS). …

High-throughput drug screening reveals Pyrvinium pamoate as effective candidate against pediatric MLL-rearranged acute myeloid leukemia.

Pediatric MLL-rearranged acute myeloid leukemia (AML) has a generally unfavorable outcome, primarily due to relapse and drug resistance. To overcome these difficulties, new therapeutic agents are urgently needed. Yet, implementing novel drugs for clinical use is a time-consuming, laborious, costly and high-risk process. Therefore, we applied a drug-repositioning strategy by screening drug libraries, comprised of >4000 compounds that are mostly FDA-approved, in a high-throughput format on primary MLL-rearranged AML cells. Here we identified pyrvinium pamoate (pyrvinium) as a novel candidate dru

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… Mebendazole, another anthelmintic drug which also showed pre-clinical efficacy in diverse human cancers, is currently being evaluated in clinical trials against pediatric brain tumors and already has a demonstrated safety profile in a Phase I trial for adults with brain tumors ( NCT02644291 ). …

Acute myeloid leukemia: from NGS, through scRNA-seq, to CAR-T. dissect cancer heterogeneity and tailor the treatment.

Acute myeloid leukemia (AML) is a malignant blood cancer with marked cellular heterogeneity due to altered maturation and differentiation of myeloid blasts, the possible causes of which are transcriptional or epigenetic alterations, impaired apoptosis, and excessive cell proliferation. This neoplasm has a high rate of resistance to anticancer therapies and thus a high risk of relapse and mortality because of both the biological diversity of the patient and intratumoral heterogeneity due to the acquisition of new somatic changes. For more than 40 years, the old gold standard "one size fits all"

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… Further in vitro research lines have revealed that synthetic Benzimidazole Mebendazole (MBZ) mediates its anti-leukemic effects via the inhibition of HSP70/90 chaperone activity and the promotion of the degradation of GLI transcription factors by the proteasome pathway [ 81 ]. … Mebendazole mediates proteasomal degradation of GLI transcription factors in Acute myeloid leukemia. Int J Mol Sci 22, (2021). 82. Hasserjian RP. Revealing the dark secrets of TP53-mutated AML. Blood. 2022;140:8–10. doi: 10.1182/blood.2022016593. 83. Tashakori M, et al. …

Identification of broad anti-coronavirus chemical agents for repurposing against SARS-CoV-2 and variants of concern.

Endemic human coronaviruses (hCoVs) 229E and OC43 cause respiratory disease with recurrent infections, while severe acute respiratory syndrome (SARS)-CoV-2 spreads across the world with impact on health and societies. Here, we report an image-based multicycle infection procedure with α-coronavirus hCoV-229E-eGFP in an arrayed chemical library screen of 5440 clinical and preclinical compounds. Toxicity counter selection and challenge with the β-coronaviruses OC43 and SARS-CoV-2 in tissue culture and human airway epithelial explant cultures (HAEEC) identified four FDA-approved compounds with ora

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… ✔ | | | | | Geldanamycin | | ✔ | | | | GPP-78 | ✔ | ✔ | ✔ | | | ✔ GSK 3 Inhibitor IX | ✔ | ✔ | | | | ✔ GZD824 | ✔ | ✔ | | | | ✔ Isavuconazole | ✔ | | | | | JTE-013 | ✔ | ✔ | | | | LE-135 | ✔ | ✔ | | | | Lomefloxacin HCl | | | | | | LY2090314 | | ✔ | | ✔ | | Mebendazole … anti-fungal agents and compounds interfering with cholesterol biosynthesis have broad effects against coronaviruses The azole-based antifungal drugs POS and Ravuconazole were effective in cell culture and HAEEC against coronaviruses, including SARS-CoV-2 infection, along with the azole-based antifungals, Mebendazole …

Aminoquinolines as Translational Models for Drug Repurposing: Anticancer Adjuvant Properties and Toxicokinetic-Related Features.

The indiscriminate consumption of antimalarials against coronavirus disease-2019 emphasizes the longstanding clinical weapons of medicines. In this work, we conducted a review on the antitumor mechanisms of aminoquinolines, focusing on the responses and differences of tumor histological tissues and toxicity related to pharmacokinetics. This well-defined analysis shows similar mechanistic forms triggered by aminoquinolines in different histological tumor tissues and under coexposure conditions, although different pharmacological potencies also occur. These molecules are lysosomotropic amines th

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… infection, also exhibits synergistic effects against human cervical cancer cells [ 20 ]; sildenafil, which failed in phase II clinical trials for angina disorders, has been redirected to the treatment of erectile dysfunctions and sensitizes prostate cancer cells to doxorubicin-mediated apoptosis [ 21 ]; mebendazole … Repurposing screen identifies mebendazole as a clinical candidate to synergise with docetaxel for prostate cancer treatment. British Journal of Cancer. 2020;122(4):517–527. doi: 10.1038/s41416-019-0681-5. 23. Yuan F., Cheng C., Xiao F., Liu H., Cao S., Zhou G. …

Наркотики, основанные на сходстве генных экспрессионных сигнатур, чтобы исследовать потенциальные признаки кексетина: тематическое исследование множественных склерозов.

Quercetin (QR) — природный флавонол, широко распространенный в королевстве растений с обширными фармакологическими последствиями. Чтобы найти потенциальные клинические показатели QR, 156 Дифференциально выраженные гены (DEG), регулируемые QR, были получены из базы данных Gene Express Omnibus, и новые потенциальные фармакологические эффекты и клинические показатели QR были перенаправлены путем интегрирования соединений с аналогичными генными сигнатурами возмущения и соответствующими сигнатурами болезни QR на основе карты связи и платформ Coexedia. Предлагаемые результаты QR оказывают главным об

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… Some scholars have successfully applied CMap to drug repurposing and found that benzimidazole compounds (flubendazole, mebendazole, and benzimidazole) may be potential candidates for the treatment of glioblastoma multiforme. …

Progress on new drug treatments for hepatic echinococcosis.

Echinococcosis: is a zoonotic parasitic disease caused by infection with the larvae of Echinococcus tapeworms. At present, the standardized treatment regimen for this disease consists of radical lesion resection combined with albendazole. For patients who are inoperable or experience postoperative recurrence, the treatment with anti-echinococcosis drugs is particularly crucial. To date, albendazole remains the primary drug clinically used for anti-echinococcosis treatment. However, it has inherent drawbacks such as low bioavailability, poor solubility, long treatment course, and multiple adver

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… Investigating the therapeutic effects of albendazole, mebendazole, and praziquantel nanocapsules in hydatid cyst-infected mice. Pathogens 14 (3), 240. 10.3390/pathogens14030240 Solomon N., Kachani M., Zeyhle E., Macpherson C. N. L. (2017). …

Repurposing Drugs in Oncology (ReDO)-diclofenac as an anti-cancer agent.

Diclofenac (DCF) is a well-known and widely used non-steroidal anti-inflammatory drug (NSAID), with a range of actions which are of interest in an oncological context. While there has long been an interest in the use of NSAIDs in chemoprevention, there is now emerging evidence that such drugs may have activity in a treatment setting. DCF, which is a potent inhibitor of COX-2 and prostaglandin E2 synthesis, displays a range of effects on the immune system, the angiogenic cascade, chemo- and radio-sensitivity and tumour metabolism. Both pre-clinical and clinical evidence of these effects, in mul

Drug repurposing: A novel strategy to target cancer stem cells and therapeutic resistance.

Chemotherapy is an effortless and frequently used approach in cancer therapy. However, in most cases, it can only prolong life expectancy and does not guarantee a complete cure. Furthermore, chemotherapy is associated with severe adverse effects, one of the major complications of effective cancer therapy. In addition, newly published research outputs show that cancer stem cells are involved in cancer disease progression, drug resistance, metastasis, and recurrence and that they are functional in the trans-differentiation capacity of cancer stem cells to cancer cells in response to treatments.

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… . | Inhibit AKT/mTOR signaling pathway; reverses chemoresistance induced by P-glycoprotein, regulating the signal transduction pathways of Hdhg, inhibiting angiogenesis and lymphangiogenesis of cancer cells. 210 24 | Mebendazole | Anti-fungal | Non-small cell lung cancer, breast cancer cells | Tubulin …

2020 ACVIM Forum On Demand Research Abstract Program.

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… (ACVIM Resident Research Award eligible) N06 | Amy Yanke | Pharmacokinetics of Mebendazole in Canine Plasma and Cerebrospinal Fluid: A Pilot Study N07 | Yoonhoi Koo | Evaluation of Serum High‐Mobility Group Box 1 Concentration in Dogs with Epilepsy N08 | Dawn Boothe | Cannabidiol Disposition After Single …

Drug prioritization identifies panobinostat as a tailored treatment element for patients with metastatic hepatoblastoma.

BACKGROUND: Patients with metastatic hepatoblastoma are treated with severely toxic first-line chemotherapies in combination with surgery. Yet, inadequate response of lung metastases to neo-adjuvant chemotherapy still compromises patient outcomes making new treatment strategies, tailored to more efficient lung clearance, mandatory. METHODS: We harnessed a comprehensive patient-derived xenograft platform and a variety of in vitro and in vivo assays to establish the preclinical and biological rationale for a new drug for patients with metastatic hepatoblastoma. RESULTS: The testing of a librar

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… Although most new compounds on the testing platform had only a minimal or moderate effect, we identified the group of microtubule-targeting agents (paclitaxel, vinorelbine, vinblastine, docetaxel, and mebendazole) as well as histone deacetylase (HDAC) inhibitors (panobinostat, rhomidepsin, quisinostat …

Beta-blockers disrupt mitochondrial bioenergetics and increase radiotherapy efficacy independently of beta-adrenergic receptors in medulloblastoma.

BackgroundMedulloblastoma is the most frequent brain malignancy of childhood. The current multimodal treatment comes at the expense of serious and often long-lasting side effects. Drug repurposing is a strategy to fast-track anti-cancer therapy with low toxicity. Here, we showed the ability of β-blockers to potentiate radiotherapy in medulloblastoma with bad prognosis.MethodsMedulloblastoma cell lines, patient-derived xenograft cells, 3D spheroids and an innovative cerebellar organotypic model were used to identify synergistic interactions between β-blockers and ionising radiations. Gene expre

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… Garancher A Lin CY Morabito M NRL and CRX define photoreceptor identity and reveal subgroup-specific dependencies in medulloblastoma Cancer Cell 33 3 2018 435 449.e6 29533784 10.1016/j.ccell.2018.02.006 PMC6368680 28 Ariey-Bonnet J Carrasco K Le Grand M In silico molecular target prediction unveils mebendazole …

The Redox Paradox of Natural Supplements in Cancer: A Narrative Review to Guide Clinical Practice.

Supplements are widely perceived as safe and beneficial; yet in oncology, this assumption is questionable. Clinical trials over the past few decades have often produced disappointing results, raising a critical question: are these agents used correctly, or could they inadvertently cause harm? This review examines supplements frequently used in cancer care-such as oral vitamin C, berberine, N-acetylcysteine, vitamin D, vitamin E, melatonin, polyphenols, alpha-lipoic acid, selenium, and coenzyme Q10-which can act as tumor suppressors or promoters depending on dose, route, and disease stage. We e

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… In non-small cell lung cancer, NAC inhibited mebendazole-induced ROS in two different cell lines [ 226 ]. Similar results are observed with vitamin C and NAC, in thyroid and breast cancer cell lines [ 30 , 207 ]. …