Xenon gas is considered to be a safe anesthetic and imaging agent. Research on its other potentially beneficial effects suggests that xenon may have broad efficacy for treating health disorders. A number of reviews on xenon applications have been published, but none have focused on substance use disorders. Accordingly, we review xenon effects and targets relevant to the treatment of substance use disorders, with a focus on opioid use disorder and alcohol use disorder. We report that xenon inhaled at subsedative concentrations inhibits conditioned memory reconsolidation and opioid withdrawal symptoms. We review work by others reporting on the antidepressant, anxiolytic, and analgesic properties of xenon, which could diminish negative affective states and pain. We discuss research supporting the possibility that xenon could prevent analgesic- or stress-induced opioid tolerance and, by so doing could reduce the risk of developing opioid use disorder. The rapid kinetics, favorable safety and side effect profiles, and multitargeting capability of xenon suggest that it could be used as an ambulatory on-demand treatment to rapidly attenuate maladaptive memory, physical and affective withdrawal symptoms, and pain drivers of substance use disorders when they occur. Xenon may also have human immunodeficiency virus and oncology applications because its effects relevant to substance use disorders could be exploited to target human immunodeficiency virus reservoirs, human immunodeficiency virus protein-induced abnormalities, and cancers. Although xenon is expensive, low concentrations exert beneficial effects, and gas separation, recovery, and recycling advancements will lower xenon costs, increasing the economic feasibility of its therapeutic use. More research is needed to better understand the remarkable repertoire of effects of xenon and its potential therapeutic applications.

Moonlighting enzymes are multifunctional proteins that perform multiple functions beyond their primary role as catalytic enzymes. Extensive research and clinical practice have demonstrated their pivotal roles in the development and progression of cancer, making them promising targets for drug development. This article delves into multiple notable moonlighting enzymes, including GSK-3, GAPDH, and ENO1, and with a particular emphasis on an enigmatic phosphatase, PTP4A3. We scrutinize their distinct roles in cancer and the mechanisms that dictate their ability to switch roles. Lastly, we discuss the potential of an innovative approach to develop drugs targeting these moonlighting enzymes: target protein degradation. This strategy holds promise for effectively tackling moonlighting enzymes in the context of cancer therapy.

In recent decades, a significant body of research has focused on targeted therapies for the treatment of central nervous system (CNS) tumors to enhance the effectiveness of management strategies. However, most of these efforts have been centered in high-income countries, which renders the generalizability of their results to low- and middle-income countries questionable. Therefore, in this review, we systematically investigated the status of research conducted on targeted therapy for CNS tumors in low- and lower-middle-income countries to elucidate the contribution of these countries in advancing neuro-oncology.

A systematic search of 3 databases was performed using a predefined search strategy. After screening the articles based on our inclusion/exclusion criteria, the data were extracted to a predesigned Excel worksheet.

A review of 44 included studies showed that India, Iran, and Lebanon were the only countries with a contribution to this field. All included studies were laboratory or animal experiments, and there were no clinical studies in this field. The most investigated CNS tumor was malignant glioma, and gene-targeted therapy was the most investigated category of targeted therapies in these countries.

Low- and lower-middle-income countries comprise more than half of the world population, but they are deprived of targeted therapies against CNS tumors. Although there are basic experiments performed on this subject, they originate in a limited number of these countries. Therefore, targeted therapy is in its preliminary stage in these countries.

To study the effect of inhibitor of differentiation 3 (ID3) on radiotherapy in patients with rectal cancer and to explore its primary mechanism.

Cell proliferation and clonogenic assays were used to study the relationship between ID3 and radiosensitivity. Co-immunoprecipitation and immunofluorescence were performed to analyze the possible mechanism of ID3 in the radiosensitivity of colorectal cancer. At the same time, a xenograft tumor model of HCT116 cells in nude mice was established to study the effect of irradiation on the tumorigenesis of ID3 knockdown colorectal cancer cells in vivo. Immunohistochemistry was performed to analyze the relationship between ID3 expression and the efficacy of radiotherapy in 46 patients with rectal cancer.

Proliferation and clonogenic assays revealed that the radiosensitivity of colorectal cancer cells decreased with ID3 depletion through p53-independent pathway. With the decrease in ID3 expression, MDC1 was downregulated. Furthermore, the expression of ID3, MDC1, and γH2AX increased and formed foci after irradiation. ID3 interacted with PPARγ and form a positive feedback loop to enhance the effect of ID3 on the radiosensitivity of colorectal cancer. Irradiation tests in nude mice also confirmed that HCT116 cells with ID3 knockdown were more affected by irradiation. Immunohistochemical study showed that rectal cancer patients with low expression of ID3 had better radiotherapy efficacy.

ID3 and PPARγ influence the radiosensitivity of colorectal cancer cells by interacting with MDC1 to form a positive feedback loop that promotes DNA damage repair. Patients with low expression of ID3 who received neoadjuvant chemoradiotherapy can obtain a better curative effect.

Despite being extensively studied for several decades, the microtubule-associated protein Tau has not finished revealing its secrets. For long, Tau has been known for its ability to promote microtubule assembly. A less known feature of Tau is its capability to bind to cancer-related protein kinases, suggesting a possible role of Tau in modulating microtubule-independent cellular pathways that are associated with oncogenesis. With the intention of finding new therapeutic targets for cancer, it appears essential to examine the interaction of Tau with these kinases and their consequences. This review aims at collecting the literature data supporting the relationship between Tau and cancer with a particular focus on glioblastoma tumors in which the pathological significance of Tau remains largely unexplored. We will first treat this subject from a mechanistic point of view showing the pivotal role of Tau in oncogenic processes. Then, we will discuss the involvement of Tau in dysregulating critical pathways in glioblastoma. Finally, we will outline promising strategies to target Tau protein for the therapy of glioblastoma.

Glycogen synthase kinase-3β (GSK-3β) is a target enzyme considered for the treatment of multiple human diseases, from neurodegenerative pathologies to viral infections and cancers. Numerous inhibitors of GSK-3β have been discovered but thus far only a few have reached clinical trials and only one drug, tideglusib (1), has been registered. Natural products targeting GSK-3β have been identified, including the two anticancer limonoids obacunone (5) and gedunin (4), both presenting a furyl-δ-lactone core. To help identifying novel GSK-3β ligands, we have performed a molecular docking study with 15 complementary natural products bearing a furyl-δ-lactone unit (such as limonin (6) and kihadanins A (8) and B (9)) or a closely related structure (such as cedrelone (10) and nimbolide (11)). The formation of GSK-3β-binding complexes for those natural products was compared to reference GSK-3β ATP-competitive inhibitors LY2090314 (3) and AR-A014418 (2). Our in silico analysis led to the identification of two new GSK-3β-binding natural products: kihadanin B (9) and nomilin (7). The latter surpassed the reference compounds in terms of calculated empirical energy of interaction (ΔE). Nomilin (7) can possibly bind to the active site of GSK-3β, notably via the furyl-δ-lactone core and its 1-acetyl group, implicated in the protein interaction. Compound structure-binding relationships are discussed. The study should help the discovery of novel natural products targeting GSK-3β.

Brain tumors in adults may be infrequent when compared with other cancer etiologies, but they remain one of the deadliest with bleak survival rates. Current treatment modalities encompass surgical resection, chemotherapy, and radiotherapy. However, increasing resistance rates are being witnessed, and this has been attributed, in part, to cancer stem cells (CSCs). CSCs are a subpopulation of cancer cells that reside within the tumor bulk and have the capacity for self-renewal and can differentiate and proliferate into multiple cell lineages. Studying those CSCs enables an increasing understanding of carcinogenesis, and targeting CSCs may overcome existing treatment resistance. One approach to weaponize new drugs is to target these CSCs through drug repurposing which entails using drugs, which are Food and Drug Administration-approved and safe for one defined disease, for a new indication. This approach serves to save both time and money that would otherwise be spent in designing a totally new therapy. In this review, we will illustrate drug repurposing strategies that have been used in brain tumors and then further elaborate on how these approaches, specifically those that target the resident CSCs, can help take the field of drug repurposing to a new level.

Introduction: Treatments for brain cancer have radically evolved in the past decade due to a better understanding of the interplay between the immune system and tumors of the central nervous system (CNS). However, glioblastoma multiforme (GBM) remains the most common and lethal CNS malignancy affecting adults.Areas covered: The authors review the literature on glioblastoma pharmacologic therapies with a focus on trials of combination chemo-/immunotherapies and drug delivery platforms from 2015 to 2021.Expert opinion: Few therapeutic advances in GBM treatment have been made since the Food and Drug Administration (FDA) approval of the BCNU-eluting wafer, Gliadel, in 1996 and oral temozolomide (TMZ) in 2005. Recent advances in our understanding of GBM have promoted a wide assortment of new therapeutic approaches including combination therapy, immunotherapy, vaccines, and Car T-cell therapy along with developments in drug delivery. Given promising preclinical data, these novel pharmacotherapies for the treatment of GBM are currently being evaluated in various stages of clinical trials.

Neuroblastoma (NB) is a heterogeneous solid tumor of the pediatric population that originates from neural crest cells and affects the developing sympathetic nervous system. It is the most common neuroblastic tumor accounting for approximately 10% of all childhood cancers and 10-15% of pediatric tumor mortalities. The outcomes range from spontaneous tumor regression in low-risk groups to metastasis and death even after multimodal therapy in high-risk groups. Hence, the detection of NB at an early stage improves outcomes and provides a better prognosis for patients. Early detection and prognosis of NB depend on specific molecules termed biomarkers which can be tissue-specific or circulating. Certain biomarkers are employed in the classification of NB into different groups to improve the treatment and prognosis, and others can be used as therapeutic targets. Therefore, novel biomarker discovery is essential for the early detection of NB, predicting the course of the disease, and developing new targeted treatment strategies. In this review, we aim to summarize the literature pertinent to some important biomarkers of NB and discuss the prognostic role of these biomarkers as well as their potential role in targeted therapy.

Central nervous system (CNS) tumors are a variety of distinct neoplasms that present multiple challenges in terms of treatment and prognosis. Glioblastoma, the most common primary tumor in adults, is associated with poor survival and remains one of the least treatable neoplasms. These tumors are highly heterogenous and complex in their nature. Due to this complexity, traditional cell culturing techniques and methods do not provide an ideal recapitulating model for the study of these tumors' behavior in vivo. Two-dimensional models lack the spatial arrangement, the heterogeneity in cell types, and the microenvironment that play a large role in tumor cell behavior and response to treatment. Recently, scientists have turned towards three-dimensional culturing methods, namely spheroids and organoids, as they have been shown to recapitulate tumors in a more faithful manner to their in vivo counterparts. Moreover, tumor-on-a-chip systems have lately been employed in CNS tumor modeling and have shown great potential in both studying the pathophysiology and therapeutic testing. In this review, we will discuss the current available literature on in vitro three-dimensional culturing models in CNS tumors, in addition to presenting their advantages and current limitations. We will also elaborate on the future implications of these models and their benefit in the clinical setting.

Medulloblastoma (MB) is the most common pediatric brain malignancy, with a 5-year overall survival (OS) rate of around 65%. The conventional MB treatment, comprising surgical resection followed by irradiation and adjuvant chemotherapy, often leads to impairment in normal body functions and poor quality of life, especially with the increased risk of recurrence and subsequent development of secondary malignancies. The development and progression of MB are facilitated by a variety of immune-evading mechanisms such as the secretion of immunosuppressive molecules, activation of immunosuppressive cells, inhibition of immune checkpoint molecules, impairment of adhesive molecules, downregulation of the major histocompatibility complex (MHC) molecules, protection against apoptosis, and activation of immunosuppressive pathways. Understanding the tumor-immune relationship in MB is crucial for effective development of immune-based therapeutic strategies. In this comprehensive review, we discuss the immunological aspect of the brain, focusing on the current knowledge tackling the mechanisms of MB immune suppression and evasion. We also highlight several key immunotherapeutic approaches developed to date for the treatment of MB.