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Targeting Cancer Through Thymoquinone: From Molecular Mechanisms to Clinical Prospects.

Thymoquinone (TQ), the active compound in Nigella sativa (black seed), has shown promising effects against cancer in many laboratory studies. In this review, we explore how TQ works on different aspects of cancer, from stopping cancer cell growth and spread, to triggering cancer cell death, reducing inflammation, and helping the immune system fight back. We also highlight how TQ may overcome one of the biggest problems in cancer treatment-chemoresistance. When used together with common treatments like chemotherapy, radiation, or immunotherapy, TQ has been shown to improve their effects and red

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… Conversely, in some glioblastoma models (U87MG, Gli36ΔEGFR), TQ inhibits autophagy (reduced Beclin-1 and ATG7 expression) and promotes lysosomal membrane permeabilization with cathepsin-B release, thereby sensitizing cells to temozolomide and favoring non-autophagic death pathways [ 43 ]. …

Exploring microRNA targeting as a promising approach for solid tumor treatment.

The discovery of microRNAs (miRNAs) and their pivotal role in gene regulation has opened up new avenues for innovative cancer treatments. Recent years have witnessed extensive research into the intricate mechanisms of miRNAs and their impact on solid tumors. These small non-coding RNA molecules are central to gene regulation and are frequently dysregulated in various cancers, particularly solid tumors. Dysregulation of specific miRNAs can initiate, progress, and metastasize tumors, making them appealing targets in cancer therapy. This article explores recent studies on identifying specific miR

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… Although it has not yet entered clinical trials, its combination with temozolomide significantly and safely prolonged survival in an orthotopic mouse model of glioblastoma multiforme ( 101 ). …

Anticancer peptides as novel immunomodulatory therapeutic candidates for cancer treatment.

Cancer remains a concern after years of research in this field. Conventional therapies such as chemotherapy, radiation, and surgery are available for cancer treatment, but they are characterized by various side effects. There are several immunological challenges that make it difficult for the immune system and conventional therapies to treat cancer. Some of these challenges include heterogeneity, resistance to medicines, and cancer relapse. Even advanced treatments like immune checkpoint inhibitors (ICIs), which revolutionized cancer treatment, have associated toxicity and resistance further n

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… Anticancer Effect of Cathelicidin LL-37, Protegrin PG-1, Nerve Growth Factor NGF, and Temozolomide: Impact on the Mitochondrial Metabolism, Clonogenic Potential, and Migration of Human U251 Glioma Cells. Molecules. 2022;27:4988. doi: 10.3390/molecules27154988. 107. …

Application of Nanoparticles for Magnetic Hyperthermia for Cancer Treatment-The Current State of Knowledge.

Hyperthermia (HT) is an anti-cancer therapy commonly used with radio and chemotherapies based on applying heat (39-45 °C) to inhibit tumor growth. However, controlling heat towards tumors and not normal tissues is challenging. Therefore, nanoparticles (NPs) are used in HT to apply heat only to tumor tissues to induce DNA damage and the expression of heat shock proteins, which eventually result in apoptosis. The aim of this review article is to summarize recent advancements in HT with the use of magnetic NPs to locally increase temperature and promote cell death. In addition, the recent develop

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… Temozolomide encapsulated and folic acid decorated chitosan nanoparticles for lung tumor targeting: Improving therapeutic efficacy both in vitro and in vivo. Oncotarget. 2017;8:111318–111332. doi: 10.18632/oncotarget.22791. 88. …

Monitoring concentration and lipid signature of plasma extracellular vesicles from HR+ metastatic breast cancer patients under CDK4/6 inhibitors treatment.

Extracellular vesicles (EVs) are cell-derived small membrane structures that transport various molecules. They have emerged as potential circulating biomarkers for monitoring responses to cancer therapies. This study aimed to comprehensively characterize plasma-carried EVs in hormone receptor-positive (HR+) metastatic breast cancer (MBC) patients treated with first-line CDK4/6 inhibitors (iCDK4/6) combined with endocrine therapy. MBC patients were classified into three groups based on their response to therapy: resistant, intermediate or sensitive. In a prospective cohort, we monitored the con

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… Temozolomide affects extracellular vesicles released by glioblastoma cells . Biochimie , 155 , 11 – 15 . 10.1016/j.biochi.2018.02.007 29454008 Becker , A. , Thakur , B. K. , Weiss , J. M. , Kim , H. S. , Peinado , H. , & Lyden , D. ( 2016 ). …

The critical role of γ-secretase and its inhibitors in cancer and cancer therapeutics.

As a multi-substrate transmembrane protease, γ-secretase exists widely in various cells. It controls multiple important cellular activities through substrate cleavage. γ-secretase inhibitors (GSIs) play a role in cancer inhibition by blocking Notch cleavage, and are considered as potential therapeutic strategies for cancer. Currently, GSIs have encouraging performance in preclinical models, yet this success does not translate well in clinical trials. In recent years, a number of breakthrough discoveries have shown us the promise of targeting γ-secretase for the treatment of cancer. Here, we in

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… . | PMID: 21825264 116 | RO4929097 +Bevacizumab | I | Patient was 18 years or older, had histologically proven malignant glioma, and progressed after radiotherapy and chemotherapy with temozolomide. | RO4929097 was taken orally for 3 days on/4 days off each week for 4 consecutive cycles (days 1-3, 8 …

ASENT 2022 Annual Meeting.

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… XPORT-GBM-029 ( NCT04421378 ) is a phase 1 dose finding study followed by an open-label randomized phase 2, 3-arm trial to evaluate SEL in combination with standard therapies for newly diagnosed and recurrent GBM (n = 350): Arm A– radiation ± SEL; Arm B– radiation and temozolomide ± SEL; Arm C – lomustine …

Noncoding RNAs related to the hedgehog pathway in cancer: clinical implications and future perspectives.

Cancer is a type of malignant affliction threatening human health worldwide; however, the molecular mechanism of cancer pathogenesis remains to be elusive. The oncogenic hedgehog (Hh) pathway is a highly evolutionarily conserved signaling pathway in which the hedgehog-Patched complex is internalized to cellular lysosomes for degradation, resulting in the release of Smoothened inhibition and producing downstream intracellular signals. Noncoding RNAs (ncRNAs) with diversified regulatory functions have the potency of controlling cellular processes. Compelling evidence reveals that Hh pathway, ncR

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… Temozolomide resistance in glioblastoma occurs by miRNA-9-targeted PTCH1, independent of sonic hedgehog level. Oncotarget. 2015;6:1190–1201. doi: 10.18632/oncotarget.2778. 126. Miao X, Gao H, Liu S, Chen M, Xu W, Ling X, et al. …

Antitumoral Effects of Tricyclic Antidepressants: Beyond Neuropathic Pain Treatment.

Growing evidence shows that nerves play an active role in cancer development and progression by altering crucial molecular pathways and cell functions. Conversely, the use of neurotropic drugs, such as tricyclic antidepressants (TCAs), may modulate these molecular signals with a therapeutic purpose based on a direct antitumoral effect and beyond the TCA use to treat neuropathic pain in oncology patients. In this review, we discuss the TCAs' safety and their central effects against neuropathic pain in cancer, and the antitumoral effects of TCAs in in vitro and preclinical studies, as well as in

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… Imipramine impedes glioma progression by inhibiting YAP as a Hippo pathway independent manner and synergizes with temozolomide. J. Cell. Mol. Med. 2021;25:9350–9363. doi: 10.1111/jcmm.16874. 57. Jeon S.H., Kim S.H., Kim Y., Kim Y.S., Lim Y., Lee Y.H., Shin S.Y. …

Role of PET/CT and Therapy Management of Pancreatic Neuroendocrine Tumors.

Pancreatic neuroendocrine neoplasms (panNENs) are heterogeneous neoplasms with neuroendocrine differentiation that show peculiar clinical and histomorphological features, with variable prognosis. In recent years, advances in knowledge regarding the pathophysiology and heterogeneous clinical presentation, as well as the availability of different diagnostic procedures for panNEN diagnosis and novel therapeutic options for patient clinical management, has led to the recognition of the need for an active multidisciplinary discussion for optimal patient care. Molecular imaging with positron emissio

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… Capecitabine-Temozolomide (CAPTEM) in advanced Grade 2 and grade 3 Neuroendocrine neoplasms (NENs)—Benefits of chemotherapy in NENs with significant 18FDG uptake. Neuroendocrinology. 2020 doi: 10.1159/000511987. 74. …

Optimal Control Theory for Personalized Therapeutic Regimens in Oncology: Background, History, Challenges, and Opportunities.

Optimal control theory is branch of mathematics that aims to optimize a solution to a dynamical system. While the concept of using optimal control theory to improve treatment regimens in oncology is not novel, many of the early applications of this mathematical technique were not designed to work with routinely available data or produce results that can eventually be translated to the clinical setting. The purpose of this review is to discuss clinically relevant considerations for formulating and solving optimal control problems for treating cancer patients. Our review focuses on two of the mo

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… Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 2005;352:987–996. doi: 10.1056/NEJMoa043330. 20. Morgan S., Hoffman K., Loblaw D.A., Buyyounouski M.K., Patton C., Barocas D., Bentzen S., Chang M., Efstathiou J., Greany P., et al. …

FDA approved drugs with pharmacotherapeutic potential for SARS-CoV-2 (COVID-19) therapy.

In December 2019, a novel SARS-CoV-2 coronavirus emerged, causing an outbreak of life-threatening pneumonia in the Hubei province, China, and has now spread worldwide, causing a pandemic. The urgent need to control the disease, combined with the lack of specific and effective treatment modalities, call for the use of FDA-approved agents that have shown efficacy against similar pathogens. Chloroquine, remdesivir, lopinavir/ritonavir or ribavirin have all been successful in inhibiting SARS-CoV-2 in vitro. The initial results of a number of clinical trials involving various protocols of administr

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… Simvastatin increases temozolomide-induced cell death by targeting the fusion of autophagosomes and lysosomes. FEBS J. 2020;287(5):1005–1034. doi: 10.1111/febs.15069. Sriram K., Insel P.A. Risks of ACE inhibitor and ARB usage in COVID-19: evaluating the evidence. Clin. Pharmacol. …

Journey of TRAIL from Bench to Bedside and its Potential Role in Immuno-Oncology.

Induction of apoptosis in cancer cells has increasingly been the focus of many therapeutic approaches in oncology field. Since its identification as a TNF family member, TRAIL (TNF-related apoptosis-inducing ligand) paved a new path in apoptosis inducing cancer therapies. Its selective ability to activate extrinsic and intrinsic cell death pathways in cancer cells only, independently from p53 mutations responsible for conventional therapeutics resistance, spotted TRAIL as a potent cancer apoptotic agent. Many recombinant preparations of TRAIL and death receptor targeting monoclonal antibodies

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… Arafat WO Anderson J Welaya K Triple therapy using radiation therapy (RT), Temozolomide (TMZ), and TRAIL agonist (TRA-8) enhances cell killing in primary glioma cancer stem cells associated with changes in distinct tyrosine kinase signaling cascades identified through kinomic analysis . …

Emerging mechanism and therapeutic potential of neurofibromatosis type 1-related nerve system tumor: Advancing insights into tumor development.

Neurofibromatosis Type 1 (NF1) is a genetic disorder resulting from mutations in the NF1 gene, which increases susceptibility to various nervous system tumors, including plexiform neurofibromas, malignant peripheral nerve sheath tumors, and optic pathway gliomas. Recent research has shown that these tumors are intricately connected to the complex, dynamic interactions within neurons, culminating in neuronal signaling that fosters tumor growth. These interactions offer crucial insights into the molecular mechanisms underpinning tumor development, as well as broader implications for therapeutic

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… , a key protein involved in the growth of TMs. 158 A clinical trial (MecMeth/NOA-24; EudraCT 2021-000708-39) is currently investigating whether inhibiting TM-dependent intercellular communication within GBM through the use of meclofenamate, a gap junction inhibitor, can enhance the effectiveness of temozolomide …

Targeted Hybrid Nanocarriers as Co-Delivery Systems for Enhanced Cancer Therapy.

Hybrid nanocarriers have realized a growing interest in drug delivery research because of the potential of being able to treat, manage or cure diseases that previously had limited therapy or cure. Cancer is currently considered the second leading cause of death globally. This makes cancer therapy a major focus in terms of the need for efficacious and safe drug formulations that can be used to reduce the rate of morbidity and mortality globally. The major challenge encountered over the years with cancer chemotherapy is the non-selectivity of anticancer drugs, leading to severe adverse effects i

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… Classes of drugs | Examples in each Class | Target site | Mechanism of action | Organ/cancer Alkylating agents* | Altretamine, bendamustine, busulfan, carboplatin, carmustine, chlorambucil, cisplatin, cyclophosphamide, dacarbazine, ifosfamide, melphalan, oxaliplatin, temozolomide | Nucleus | Destroys …

Histone Deacetylase Inhibitors in Pediatric Brain Cancers: Biological Activities and Therapeutic Potential.

Brain cancers are the leading cause of cancer-related deaths in children. Biological changes in these tumors likely include epigenetic deregulation during embryonal development of the nervous system. Histone acetylation is one of the most widely investigated epigenetic processes, and histone deacetylase inhibitors (HDACis) are increasingly important candidate treatments in many cancer types. Here, we review advances in our understanding of how HDACis display antitumor effects in experimental models of specific pediatric brain tumor types, i.e., medulloblastoma (MB), ependymoma (EPN), pediatric

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… In a high-risk cytogenetic group 3 and molecular group C EPN model (DKFZ-EP1NS) that shows high tumorigenic potential in vivo , cells are resistant to cytotoxic chemotherapeutics temozolomide, vincristine, and cisplatin but respond to HDACi treatment ( Milde et al., 2011 ). …

Clinical Trials with Combination of Cytokine-Induced Killer Cells and Dendritic Cells for Cancer Therapy.

Adoptive cellular immunotherapy (ACI) is a promising treatment for a number of cancers. Cytokine-induced killer cells (CIKs) are considered to be major cytotoxic immunologic effector cells. Usually cancer cells are able to suppress antitumor responses by secreting immunosuppressive factors. CIKs have significant antitumor activity and are capable of eradicating tumors with few side effects. They are a very encouraging cell population used against hematological and solid tumors, with an inexpensive expansion protocol which could yield to superior clinical outcome in clinical trials employing ad

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… The standard of treatment is represented by surgical resection followed by radiotherapy and adjuvant temozolomide (TMZ). …

Peroxisome Proliferator-Activated Receptors (PPAR)γ Agonists as Master Modulators of Tumor Tissue.

In most clinical trials, thiazolidinediones do not show any relevant anti-cancer activity when used as mono-therapy. Clinical inefficacy contrasts ambiguous pre-clinical data either favoring anti-tumor activity or tumor promotion. However, if thiazolidinediones are combined with additional regulatory active drugs, so-called 'master modulators' of tumors, i.e., transcriptional modulators, metronomic low-dose chemotherapy, epigenetically modifying agents, protein binding pro-anakoinotic drugs, such as COX-2 inhibitors, IMiDs, etc., the results indicate clinically relevant communicative reprogram

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… Randomized phase II trial of chemoradiotherapy followed by either dose-dense or metronomic temozolomide for newly diagnosed glioblastoma. J. Clin. Oncol. 2009;27:3861–3867. doi: 10.1200/JCO.2008.20.7944. 75. …

Demethylating Agents in the Treatment of Cancer.

Gene silencing resulting from aberrant DNA methylation can lead to tumorigenesis. Therefore, drugs that inhibit or interfere with DNA methylation have been used to reactivate and induce silenced gene re-expression in malignancies. Two demethylating agents, azacitidine and decitabine, are approved for the treatment of myelodysplastic syndromes (MDS) by the U.S. Food and Drug Administration (FDA), and are now considered the standard of care in MDS. In this review, we discuss clinical data, including clinical benefits and toxicities, which led to the approval of azacitidine and decitabine. We als

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… MGMT gene silending and benefit from temozolomide in glioblastoma. New Engl. J. Med. 2005;352:997–1003. doi: 10.1056/NEJMoa043331. 21. Hegi M.E., Liu L., Herman J.G., Stupp R., Wick W., Weller M., Mehta M.P., Gilbert M.R. …

Late Breaking Orals.

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