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Targeting the ubiquitin-proteasome system: a novel therapeutic strategy for neuroblastoma.

Neuroblastoma (NB) stands as a common and formidable malignant tumor among children, characterized by marked tumor heterogeneity and resistance to conventional treatments. Central to the regulation of protein stability, localization, and function is the process of ubiquitination-a critical protein modification. The therapeutic potential of drugs that target deubiquitination, demonstrated in the treatment of refractory multiple myeloma, warrants investigation in the context of NB. This review endeavors to demystify the intricate biological implications of ubiquitination within NB pathology, syn

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… Another study from the Barcelona Pediatric Cancer Center explored the efficacy and safety of GD2 monoclonal combined with irinotecan and temozolomide in another regimen called Hu3F8 (H), irinotecan (I), temozolomide (T), and sargramostim (S) (HITS) for the treatment of high-risk recurrent NB. … Irinotecan, temozolomide, and dinutuximab with GM-CSF in children with refractory or relapsed neuroblastoma: A report from the children's oncology group . …

A Novel Hydroxamic Acid-Based Curcumin Derivative as Potent Histone Deacetylase Inhibitor for the Treatment of Glioblastoma.

Glioblastoma (GBM) is one of the most common primary and deadliest malignant brain tumor with chemoresistance and poor prognosis. There is a lack of effective chemotherapeutic drug for the treatment of GBM. In this work, we reported the preparation of a histone deacetylase (HDAC) inhibitor, DMC-HA, from the structural modification of natural product curcumin. DMC-HAs were tested in an HDAC inhibition assay and an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for cytotoxicity. It showed potent inhibition of HDAC1-2 and HDAC6 with IC50 values in the submicromolar conce

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… Phase I/II Trial of Vorinostat Combined With Temozolomide and Radiation Therapy for Newly Diagnosed Glioblastoma: Results of Alliance N0874/ABTC 02. Neuro Oncol (2018) 20(4):546–56. doi: 10.1093/neuonc/nox161 19. Yao H, Liu J, Xu S, Zhu Z, Xu J. … Demethoxycurcumin was Superior to Temozolomide in the Inhibition of the Growth of Glioblastoma Stem Cells In Vivo . Tumour Biol J Int Soc Oncodevelopmental Biol Med (2016) 37:15847–57. doi: 10.1007/s13277-016-5399-x 25. Shi L, Sun G, Zhang Y. …

Hypoxia within the glioblastoma tumor microenvironment: a master saboteur of novel treatments.

Glioblastoma (GBM) tumors are the most aggressive primary brain tumors in adults that, despite maximum treatment, carry a dismal prognosis. GBM tumors exhibit tissue hypoxia, which promotes tumor aggressiveness and maintenance of glioma stem cells and creates an overall immunosuppressive landscape. This article reviews how hypoxic conditions overlap with inflammatory responses, favoring the proliferation of immunosuppressive cells and inhibiting cytotoxic T cell development. Immunotherapies, including vaccines, immune checkpoint inhibitors, and CAR-T cell therapy, represent promising avenues f

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… The results demonstrated a significant improvement in both progression-free survival (6.7 months in the TTFields plus temozolomide group and 4.0 months in the temozolomide-alone group) and overall survival (median overall survival was 20.9 months in the TTFields-temozolomide group vs 16.0 months in the … Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: A randomized clinical trial . …

A systematic review of non-standard dosing of oral anticancer therapies.

BackgroundThe use of oral systemic anticancer therapies (SACT) has increased and led to improved cancer survival outcomes, particularly with the introduction of small molecule targeted agents and immunomodulators. Oral targeted SACT are, however, associated with toxicities, which might result in reduced quality of life and non-adherence. To reduce treatment-related toxicity, the practice of non-standard dosing is increasing; however guidance to govern this practice is limited. A systematic review was conducted to identify evidence of, and outcomes from, non-standard dosing of oral SACT in onco

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… The number of studies per drug investigated was as follows: sunitinib (10), imatinib (7), sorafenib (2), vemurafenib (3), dasatinib (2), lenalidomide (2), crizotinib (2), erlotinib (2), gefitinib (2), temozolomide (1) and thalidomide (1). … Data from this trial suggest that the alternating weekly schedule of temozolomide showed clinically meaningful improvement in survival outcomes compared to the registration trial (PFS rate at 6 months: 21%) [ 20 ]. …

DNA Damaging Drugs

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… Temozolomide is an imidazotetrazine derivative of dacarbazine. … Temozolomide clearance is not affected by CYP450 inducing drugs, nor does administration of temozolomide competitively inhibit the metabolism of those drugs. Temozolomide dosing may require interruption or discontinuation during concomitant radio-therapy (Table 2.2 ). …

Molecular mechanisms of resveratrol as chemo and radiosensitizer in cancer.

One of the primary diseases that cause death worldwide is cancer. Cancer cells can be intrinsically resistant or acquire resistance to therapies and drugs used for cancer treatment through multiple mechanisms of action that favor cell survival and proliferation, becoming one of the leading causes of treatment failure against cancer. A promising strategy to overcome chemoresistance and radioresistance is the co-administration of anticancer agents and natural compounds with anticancer properties, such as the polyphenolic compound resveratrol (RSV). RSV has been reported to be able to sensitize c

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… And that it can overcome the resistance to DOX and Docetaxel in this model ( Xiong et al., 2021 ). 7.3 Temozolomide (TMZ) and resveratrol Temozolomide is a chemotherapy drug that mostly treats brain tumors (GBM, medulloblastomas, neuroblastomas, and sarcomas). … Temozolomide comes in capsules and can be used alone or in combination with XRT. …

Integration of circadian rhythms and immunotherapy for enhanced precision in brain cancer treatment.

Circadian rhythms significantly impact (patho)physiological processes, with disruptions linked to neurodegenerative diseases and heightened cancer vulnerability. While immunotherapy has shown promise in treating various cancers, its efficacy in brain malignancies remains limited. This review explores the nexus of circadian rhythms and immunotherapy in brain cancer treatment, emphasising precision through alignment with the body's internal clock. We evaluate circadian regulation of immune responses, including cell localisation and functional phenotype, and discuss how circadian dysregulation af

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… of MGMT has a strong prognostic value for treatment with temozolomide. … Temozolomide chronotherapy in glioma: a systematic review Curr Oncol 30 2023 1893 1902 36826108 10.3390/curroncol30020147 PMC9955138 100 Gonzalez-Aponte M.F. Damato A.R. Trebucq L.L. …

Cell-based immunotherapy of glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most aggressive and lethal primary glial brain tumor. It has an unfavorable prognosis and relatively ineffective treatment protocols, with the median survival of patients being ~15 months. Tumor resistance to treatment is associated with its cancer stem cells (CSCs). At present, there is no medication or technologies that have the ability to completely eradicate CSCs, and immunotherapy (IT) is only able to prolong the patient's life. The present review aimed to investigate systemic solutions for issues associated with immunosuppression, such as ineffective

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… Traditionally, γ-radiation of 60 Gy is used, including 2 Gy daily at 30 fractions for 6 weeks ( 13 ), together with chemotherapy, where temozolomide (TMZ) is considered the gold standard for the treatment of GBM. … Phase I/IIa study of concomitant radiotherapy with olaparib and temozolomide in unresectable or partially resectable glioblastoma: OLA-TMZ-RTE-01 trial protocol. BMC Cancer. 2019;19:198. doi: 10.1186/s12885-019-5413-y. 17. …

Recent advances in precision oncology research.

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… The device was approved for use in combination with temozolomide (i.e., alkylating agent) chemotherapy, after surgery, chemotherapy, or radiation, for patients with newly diagnosed GBM. 20 In 2017, researchers reported longer follow-up findings from the same clinical trial. … Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma: a randomized clinical trial. JAMA. 2015;314:2535–2543. doi: 10.1001/jama.2015.16669. 21. Perry JR, et al. Short-course radiation plus temozolomide in elderly patients with glioblastoma. N. …

LAK to CIK continuum in glioma immunotherapy: a systematic review of efficacy and safety outcomes.

BACKGROUND: Immunotherapy against gliomas, including Glioblastoma multiform (GBM) as the most lethal type combines innate and adaptive immune responses to strengthen systemic and host-specific immunity. Among various cell-based immunotherapies, activated cell therapies utilize autologous immune cells activated ex vivo-such as lymphokine-activated killer (LAK) cells, cytokine-induced killer (CIK) cells, and cytotoxic T lymphocytes. Despite challenges, LAK laid the groundwork for further progress in activated killer cell therapies, such as CIK cells. CIK cells with their MHC-independent lytic ac

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… In all CIK therapy studies, therapy was given along with standard-of-care treatments, which were mostly chemotherapy and/or radiation based on temozolomide. … Synergistic therapeutic effects of cytokine-induced killer cells and temozolomide against glioblastoma. Oncol Rep. 2011;25(1):33–9. 21109954 12. …

An Overview of Advances in Rare Cancer Diagnosis and Treatment.

Cancer stands as the leading global cause of mortality, with rare cancer comprising 230 distinct subtypes characterized by infrequent incidence. Despite the inherent challenges in addressing the diagnosis and treatment of rare cancers due to their low occurrence rates, several biomedical breakthroughs have led to significant advancement in both areas. This review provides a comprehensive overview of state-of-the-art diagnostic techniques that encompass new-generation sequencing and multi-omics, coupled with the integration of artificial intelligence and machine learning, that have revolutioniz

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… Veliparib is a PARP inhibitor reported to significantly enhance the efficacy of temozolomide in glioblastoma with MGMT promoter hypermethylation [ 89 ]. … In a previous study, a combination of 60 Gy radiotherapy, temozolomide, and bevacizumab treatment prolonged the PFS but did not improve the OS in glioblastoma patients. …

Potent molecular-targeted therapies for gastro-entero-pancreatic neuroendocrine carcinoma.

Neuroendocrine neoplasms (NENs), which are characterized by neuroendocrine differentiation, can arise in various organs. NENs have been divided into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs) based on morphological differentiation, each of which has a distinct etiology, molecular profile, and clinicopathological features. While the majority of NECs originate in the pulmonary organs, extrapulmonary NECs occur most predominantly in the gastro-entero-pancreatic (GEP) system. Although platinum-based chemotherapy is the main therapeut

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… It should also be noted that temozolomide is active in pancreatic NETs [ 8 , 31 , 103 ], and a combination of capecitabine and temozolomide (CAPTEM) demonstrated a high ORR and long PFS compared to temozolomide alone [ 141 ]. … There are ongoing phase II trials of everolimus monotherapy ( NCT02113800 and NCT02687958 ) and a combination of everolimus with temozolomide ( NCT02248012 ) in NEC (Table 7 ). …

Metronomic chemotherapy.

Toxic effects and chemoresistance are major hurdles in chemotherapy and to avoid these problems caused by traditional chemotherapeutic regimens, a new modality of drug administration called "metronomic chemotherapy" has emerged. Such regimen involves the frequent administration of conventional chemotherapeutic agents at very low doses to target activated endothelial cells in tumors, the advantages of which include minimal adverse effects and a rare chance of developing acquired drug resistance. Previously it was thought that they act by targeting angiogenesis, but recently additional mechanism

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… In a study published in 2002, Sterba et al ., demonstrated the effect of metronomic temozolomide in combination with radiotherapy in children with medulloblastoma. … For example, cumulative dose of etoposide or temozolomide can lead to secondary leukemia.[ 34 35 ] Although physiologic angiogenesis differs from tumor neoangiogenesis, special attention must be given to the growth and development of young children receiving metronomic chemotherapy. …

Vincristine in Combination Therapy of Cancer: Emerging Trends in Clinics.

Treatment of blood malignancies and other cancer diseases has been mostly unfeasible, so far. Therefore, novel treatment regimens should be developed and the currently used ones should be further elaborated. A stable component in various cancer treatment regimens consists of vincristine, an antimitotic compound of natural origin. Despite its strong anticancer activity, mostly, it cannot be administered as monotherapy due to its unspecific action and severe side effects. However, vincristine is suitable for combination therapy. Multidrug treatment regimens including vincristine are standardly a

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… Besides etoposide and temozolomide, vincristine and carboplatin were tested also in combination with topotecan (Hycamtin ® , GlaxoSmithKline, London, UK), which is a topoisomerase inhibitor. … Procarbazine, lomustine and vincristine or temozolomide: Which is the better regimen? CNS Oncol. 2015 4 341 346 10.2217/cns.15.36 26544062 PMC6082332 82. Parasramka S. Talari G. Rosenfeld M. Guo J. Villano J.L. …

Oblimersen: Augmerosen, BCL-2 antisense oligonucleotide - Genta, G 3139, GC 3139, oblimersen sodium.

Oblimersen is an antisense oligonucleotide developed by Genta for systemic use as an injection. It comprises a phosphorothioate backbone lin … ting a phase I clinical trial (NCT00409383) to evaluate the combination of oblimersen, ABI 007, and temozolomide in chemotherapy-naive patients with advanced melanoma. This trial was initiated in November 2006 and is the first follow-on study to Genta's phase III trial of oblimersen plus dacarbazine. Oblimersen received orphan drug status in the US and EU for …

The Role of Cannabinoids in Advancing Cancer Treatment: Insights from Evidence-Based Medicine.

Purpose of reviewThis document critically examines the role of cannabinoids in cancer care during an era marked by rapid advancements in oncology and changing perceptions on cannabis. It traces the historical context of cannabis in medicinal use, navigating its journey from widespread acceptance, subsequent criminalization, to its resurgence in modern therapeutic applications, particularly within the framework of Evidence-Based Medicine (EBM).Recent findingsAnchored in EBM principles, this study synthesizes current research from clinical trials, systematic reviews, and meta-analyses to evaluat

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… Twelves et al. conducted a randomized, placebo-controlled trial examining the use of Nabiximols in combination with temozolomide in patients with recurrent GBM [ 64 ]. … The ARISTOCRAT trial ( NCT05629702 ) is a phase II study evaluating Nabiximols in combination with Temozolomide for recurrent glioblastoma, aiming to improve OS [ 102 ]​​. …

Metronomic chemotherapy: changing the paradigm that more is better.

The introduction of the "maximum tolerated dose" in usual treatment protocols (and its concomitant overt toxicity) made necessary the imposition of rest periods between cycles of therapy-a practice that not only involves re-growth of tumour cells, but also growth of selected clones resistant to the therapy. To avoid the problems caused by traditional chemotherapeutic regimens, a new modality of drug administration called "metronomic chemotherapy" has been proposed. This name makes reference to the chronic, equally spaced administration of (generally) low doses of various chemotherapeutic drugs

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… A pilot study of metronomic temozolomide treatment in patients with recurrent temozolomide- refractory glioblastoma. Oncol Rep. 2006;16:1117–21. 73. Coleman M, Martin P, Ruan J, et al. … Concomitant radiotherapy and metronomic temozolomide in pediatric high-risk brain tumors. Neoplasma. 2002;49:117–20. 76. Sterba J, Valik D, Mudry P, et al. …

Grading Central Diabetes Insipidus Induced by Immune Checkpoint Inhibitors: A Challenging Task.

Central diabetes insipidus (CDI) is a rare endocrine disease deriving from an insufficient production or secretion of anti-diuretic hormone. Recently, CDI has been reported as a rare side effect triggered by immune checkpoint inhibitors (ICI) in cancer patients. Despite its current rarity, CDI triggered by ICI is expected to affect an increasing number of patients because of the expanding use of these effective drugs in a growing number of solid and hematologic malignancies. An appropriate assessment of the severity of adverse events induced by anticancer agents is crucial in their management,

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… Central Diabetes Insipidus: A Previously Unreported Side Effect of Temozolomide . J Clin Endocrinol Metab ( 2013 ) 98 : 3926–31 . doi: 10.1210/jc.2013-2435 PMC3790614 23928668 14 Kuo C Foon D Waters K Cheung C Margol AS . … Central Diabetes Insipidus: A Rare Unreported Side Effect of Temozolomide in Pediatrics . Pediatr Blood Cancer ( 2020 ) 67 : e28516 . doi: 10.1002/pbc.28516 32573959 15 Mahiat C Capes A Duprez T Whenham N Duck L Labriola L . …

Dethroning of Neuroendocrine Tumor as an Orphan Disease: US Incidence, Prevalence, and Survival in the 21st Century.

Importance: Neuroendocrine tumors (NETs) have traditionally been considered rare (orphan) diseases; however, improvements in diagnostic methods and heightened awareness about NETs may have altered their epidemiologic profile in the U.S. Objective: To evaluate trends in incidence, prevalence, and survival of NETs in the United States from 2000 to 2021 using updated data from the SEER-22 registry. Method: This population-based, retrospective cohort study used the SEER-22 database for incidence, prevalence, and survival analyses. Data included 231,659 patients diagnosed with NETs between 2000 and

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… A randomized study of temozolomide or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors: A trial of the ECOG-ACRIN Cancer Research Group (E2211) J. Clin. Oncol. 2018;36:15. doi: 10.1200/JCO.2018.36.15_suppl.4004. 16. … Randomized study of temozolomide or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors (ECOG-ACRIN E2211) J. Clin. Oncol. 2023;41:1359–1369. doi: 10.1200/JCO.22.01013. 17. …

Clinical trial challenges, design considerations, and outcome measures in rare CNS tumors.

Clinical research for patients with rare cancers has been very challenging. First and foremost, patient accrual to clinical trials typically requires a network, cooperative group, or even international collaboration in order to achieve the necessary numbers of patients to adequately evaluate a new treatment or intervention. Similar limitations in preclinical models and in the understanding the natural history of the disease or pertinent prognostic factors further impede the development of hypothesis-based, appropriately powered clinical trials. However, despite these challenges, several studie

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… Fig. 3 Comparison of incidence of moderate-to-severe spine symptoms from baseline to cycle 6 of temozolomide-lapatinib treatment (negative change means fewer patients). … A phase II study of dose-dense temozolomide and lapatinib for recurrent low-grade and anaplastic supratentorial, infratentorial, and spinal cord ependymoma. Neuro Oncol. 2021;23(3):468–477. 14. Jürgensmeier JM, Eder JP, Herbst RS. …