Glioblastoma (GBM) is an aggressive and highly malignant primary brain tumor characterized by rapid growth and a poor prognosis for patients. Despite advancements in treatment, the median survival time for GBM patients remains low. One of the crucial challenges in understanding and treating GBMs involves its remarkable cellular heterogeneity and adaptability. Central to the survival and proliferation of GBM cells is their ability to undergo metabolic reprogramming. Metabolic reprogramming is a process that allows cancer cells to alter their metabolism to meet the increased demands of rapid growth and to survive in the often oxygen- and nutrient-deficient tumor microenvironment. These changes in metabolism include the Warburg effect, alterations in several key metabolic pathways including glutamine metabolism, fatty acid synthesis, and the tricarboxylic acid (TCA) cycle, increased uptake and utilization of glutamine, and more. Despite the complexity and adaptability of GBM metabolism, a deeper understanding of its metabolic reprogramming offers hope for developing more effective therapeutic interventions against GBMs.

Glioblastoma is the most common malignant primary central nervous system tumor and one of the most debilitating cancers. The prognosis of patients with glioblastoma remains poor, and the management of this tumor, both in its primary and recurrent forms, remains suboptimal. Despite the tremendous efforts that are being put forward by the research community to discover novel efficacious therapeutic agents and modalities, no major paradigm shifts have been established in the field in the last decade. However, this does not mirror the abundance of relevant findings and discoveries made in preclinical glioblastoma research. Hence, developing and utilizing appropriate preclinical models that faithfully recapitulate the characteristics and behavior of human glioblastoma is of utmost importance. Herein, we offer a holistic picture of the evolution of preclinical models of glioblastoma. We further elaborate on the commonly used in vitro and vivo models, delving into their development, favorable characteristics, shortcomings, and areas of potential improvement, which aids researchers in designing future experiments and utilizing the most suitable models. Additionally, this review explores progress in the fields of humanized and immunotolerant mouse models, genetically engineered animal models, 3D in vitro models, and microfluidics and highlights promising avenues for the future of preclinical glioblastoma research.

Cancer continues to be a prime contributor to global mortality. Despite tremendous research efforts and major advances in cancer therapy, much remains to be learned about the underlying molecular mechanisms of this debilitating disease. A better understanding of the key signaling events driving the malignant phenotype of cancer cells may help identify new pharmaco-targets. Cyclic adenosine 3′,5′-monophosphate (cAMP) modulates a plethora of biological processes, including those that are characteristic of malignant cells. Over the years, most cAMP-mediated actions were attributed to the activity of its effector protein kinase A (PKA). However, studies have revealed an important role for the exchange protein activated by cAMP (Epac) as another effector mediating the actions of cAMP. In cancer, Epac appears to have a dual role in regulating cellular processes that are essential for carcinogenesis. In addition, the development of Epac modulators offered new routes to further explore the role of this cAMP effector and its downstream pathways in cancer. In this review, the potentials of Epac as an attractive target in the fight against cancer are depicted. Additionally, the role of Epac in cancer progression, namely its effect on cancer cell proliferation, migration/metastasis, and apoptosis, with the possible interaction of reactive oxygen species (ROS) in these phenomena, is discussed with emphasis on the underlying mechanisms and pathways.

Gliomas are diffusely infiltrating brain tumors whose prognosis is strongly influenced by their extent of invasion into the surrounding brain tissue. While lower-grade gliomas present more circumscribed borders, high-grade gliomas are aggressive tumors with widespread brain infiltration and dissemination. Glioblastoma (GBM) is known for its high invasiveness and association with poor prognosis. Its low survival rate is due to the certainty of its recurrence, caused by microscopic brain infiltration which makes surgical eradication unattainable. New insights into GBM biology at the single-cell level have enabled the identification of mechanisms exploited by glioma cells for brain invasion. In this review, we explore the current understanding of several molecular pathways and mechanisms used by tumor cells to invade normal brain tissue. We address the intrinsic biological drivers of tumor cell invasion, by tackling how tumor cells interact with each other and with the tumor microenvironment (TME). We focus on the recently discovered neuronal niche in the TME, including local as well as distant neurons, contributing to glioma growth and invasion. We then address the mechanisms of invasion promoted by astrocytes and immune cells. Finally, we review the current literature on the therapeutic targeting of the molecular mechanisms of invasion.

Medulloblastoma is the most common malignant pediatric brain tumor and is associated with significant morbidity and mortality in the pediatric population. Despite the use of multiple therapeutic approaches consisting of surgical resection, craniospinal irradiation, and multiagent chemotherapy, the prognosis of many patients with medulloblastoma remains dismal. Additionally, the high doses of radiation and the chemotherapeutic agents used are associated with significant short- and long-term complications and adverse effects, most notably neurocognitive delay. Hence, there is an urgent need for the development and clinical integration of targeted treatment regimens with greater efficacy and superior safety profiles. Since the adoption of the molecular-based classification of medulloblastoma into wingless (WNT) activated, sonic hedgehog (SHH) activated, group 3, and group 4, research efforts have been directed towards unraveling the genetic, epigenetic, transcriptomic, and proteomic profiles of each subtype. This review aims to delineate the progress that has been made in characterizing the neurodevelopmental and molecular features of each medulloblastoma subtype. It further delves into the implications that these characteristics have on the development of subgroup-specific targeted therapeutic agents. Furthermore, it highlights potential future avenues for combining multiple agents or strategies in order to obtain augmented effects and evade the development of treatment resistance in tumors.