The CRISPR system is a revolutionary genome editing tool that has the potential to revolutionize the field of cancer research and therapy. The ability to precisely target and edit specific genetic mutations that drive the growth and spread of tumors has opened up new possibilities for the development of more effective and personalized cancer treatments. In this review, we will discuss the different CRISPR-based strategies that have been proposed for cancer therapy, including inactivating genes that drive tumor growth, enhancing the immune response to cancer cells, repairing genetic mutations that cause cancer, and delivering cancer-killing molecules directly to tumor cells. We will also summarize the current state of preclinical studies and clinical trials of CRISPR-based cancer therapy, highlighting the most promising results and the challenges that still need to be overcome. Safety and delivery are also important challenges for CRISPR-based cancer therapy to become a viable clinical option. We will discuss the challenges and limitations that need to be overcome, such as off-target effects, safety, and delivery to the tumor site. Finally, we will provide an overview of the current challenges and opportunities in the field of CRISPR-based cancer therapy and discuss future directions for research and development. The CRISPR system has the potential to change the landscape of cancer research, and this review aims to provide an overview of the current state of the field and the challenges that need to be overcome to realize this potential.

This systematic review aims to evaluate the influence of environmental enrichment (EE) on oncological factors in experimental studies involving various types of cancer models. A comprehensive search was conducted in three databases: PubMed (161 articles), Embase (335 articles), and Scopus (274 articles). Eligibility criteria were applied based on the PICOS strategy to minimize bias. Two independent researchers performed the searches, with a third participant resolving any discrepancies. The selected articles were analyzed, and data regarding sample characteristics and EE protocols were extracted. The outcomes focused solely on cancer and tumor-related parameters, including cancer type, description of the cancer model, angiogenesis, tumor occurrence, volume, weight, mice with tumors, and tumor inhibition rate. A total of 770 articles were identified across the three databases, with 12 studies meeting the inclusion criteria for this systematic review. The findings demonstrated that different EE protocols were effective in significantly reducing various aspects of tumor growth and development, such as angiogenesis, volume, weight, and the number of mice with tumors. Furthermore, EE enhanced the rate of tumor inhibition in mouse cancer models. This systematic review qualitatively demonstrates the impacts of EE protocols on multiple parameters associated with tumor growth and development, including angiogenesis, occurrence, volume, weight, and tumor incidence. Moreover, EE demonstrated the potential to increase the rate of tumor inhibition. These findings underscore the importance of EE as a valuable tool in the management of cancer.

To systematically review and evaluate metformin\'s potential impact on vestibular schwannoma (VS) growth.
PubMed, Cochrane Library, and Embase.
A retrospective cohort study was performed on sporadic VS patients undergoing initial observation who had at least two magnetic resonance imaging studies. Patients were stratified by metformin use during the observation period. Primary endpoint was VS growth, defined as at least a 2 mm increase in diameter. Survival free of tumor growth was evaluated between groups. Systematic review and meta-analysis were performed to produce a pooled odds ratio [OR]. Study heterogeneity was assessed and post-hoc power analysis was performed.
A total of 123 patients were included, of which 17% were taking metformin. Median patient age was 56.6 years (range, 25.1-84.5). There were no statistically significant differences between the groups. Survival analysis did not demonstrate a statistically significant difference in time to VS growth between groups (hazard ratio = 0.61, 95% confidence interval [CI] = 0.29-1.29). Furthermore, logistic regression analysis did not demonstrate a statistically significant difference between groups in the odds of VS growth (OR = 0.46, 95% CI = 0.17-1.27). Systematic review identified 3 studies. Meta-analysis suggested that metformin reduces the odds of developing VS growth (pooled OR = 0.45, 95% CI = 0.29-0.71). Studies demonstrated low between-study heterogeneity. Power analysis demonstrated a sample size of 220 patients with equal randomization would be required to prospectively identify a true difference with 80% power.
Metformin use may reduce the odds of VS growth. A randomized trial would be ideal to identify an unbiased estimate of metformin\'s effect on VS growth. Laryngoscope, 133:2066-2072, 2023.

BACKGROUND: Cancer therapies are associated with multiple adverse effects, including (but not limited to) cancer-related fatigue (CRF). Fatigue is one of the most common side effects of immune checkpoint inhibitors (ICIs), occurring in up to 25% of patients. Physical activity has been shown to help reduce CRF through modulating the immune system, and may synergistically aid in the anti-tumor effects of ICIs. This review describes the nature and scope of evidence for the effects associated with concurrent physical activity while undergoing ICI therapy.
METHODS: Scoping review methodology was utilized to identify studies, extract data, and collate and summarize results.
RESULTS: In literature published from January 2010 through to August 2021, only one human study and three pre-clinical studies met inclusion criteria.
CONCLUSIONS: Existing evidence supports that physical activity is associated with decreased treatment-related toxicities such as CRF. However, further investigation is warranted. The dearth of clinical studies illustrates the need for more research to address this question, to guide patients and their providers in the application of appropriate physical activity interventions in those patients undergoing ICI.

The extradural neural axis compartment (EDNAC) is an adipovenous zone located between the meningeal and endosteal layers of the dura and has been minimally investigated. It runs along the neuraxis from the orbits down to the coccyx and contains fat, valveless veins, arteries, and nerves. In the present review, we have outlined the current knowledge regarding the structural and functional significance of the EDNAC.
We performed a narrative review of the reported EDNAC data.
The EDNAC can be organized into 4 regional enlargements along its length: the orbital, lateral sellar, clival, and spinal segments, with a lateral sellar orbital junction linking the orbital and lateral sellar segments. The orbital EDNAC facilitates the movement of the eyeball and elsewhere allows limited motility for the meningeal dura. The major nerves and vessels are cushioned and supported by the EDNAC. Increased intra-abdominal pressure will also be conveyed along the spinal EDNAC, causing increased venous pressure in the spine and cranium. From a pathological perspective, the EDNAC functions as a low-resistance, extradural passageway that might facilitate tumor encroachment and expansion.
Clinicians should be aware of the extent and significance of the EDNAC, which could affect skull base and spine surgery, and have an understanding of the tumor spread pathways and growth patterns. Comparatively little research has focused on the EDNAC since its initial description. Therefore, future investigations are required to provide more information on this underappreciated component of neuraxial anatomy.

During the last decade, the dynamics of the cellular crosstalk have highlighted the significance of the host vs. tumor interaction. This resulted in the development of novel immunotherapeutic strategies in order to modulate/inhibit the mechanisms leading to escape of tumor cells from immune surveillance. Different monoclonal antibodies directed against immune checkpoints, e.g., the T lymphocyte antigen 4 and the programmed cell death protein 1/ programmed cell death ligand 1 have been successfully implemented for the treatment of cancer. Despite their broad activity in many solid and hematologic tumor types, only 20-40% of patients demonstrated a durable treatment response. This might be due to an impaired T cell tumor interaction mediated by immune escape mechanisms of tumor and immune cells as well as alterations in the composition of the tumor microenvironment, peripheral blood, and microbiome. These different factors dynamically regulate different steps of the cancer immune process thereby negatively interfering with the T cell -mediated anti-tumoral immune responses. Therefore, this review will summarize the current knowledge of the different players involved in inhibiting tumor immunogenicity and mounting resistance to checkpoint inhibitors with focus on the role of tumor T cell interaction. A better insight of this process might lead to the development of strategies to revert these inhibitory processes and represent the rational for the design of novel immunotherapies and combinations in order to improve their efficacy.

Background: Physical exercise is suspected to reduce cancer risk and mortality. So far, little is known about the underlying mechanisms. Although limited, murine models represent a promising attempt in order to gain knowledge in this field. Objective: A systematic review and meta-analysis examining various treatment protocols was conducted in order to determine the impact of exercise on tumor growth in rodents. Methods: PubMed, Google scholar and System for information on Gray literature in Europe were screened from inception to October 2017. Risk of bias within individual studies was assessed using the Office of Health Assessment and Translation risk of bias rating tool for human and animal trials. The effect of exercise on tumor growth over and above non-exercise control was pooled using random-effects model. Subgroup analyses were conducted to identify potential moderators. Results: The quality of the included 17 articles ranged between \"probably low\" and \"high risk of bias.\" A significant reduction in tumor growth in exercising animals compared to controls was detected (Hedges\' g = -0.40; 95% CI -0.66 to -0.14, p < 0.01) with between-study heterogeneity (τ2 = 0.217, I 2 = 70.28%, p < 0.001). The heterogeneity was partially explained by three moderators representing the in-between group differences of \"maximum daily exercise\" R 2 = 33% (p < 0.01), \"type of cancer administration\" R 2 = 28% (p < 0.05), and \"training initiation\" R 2 = 27% (p < 0.05). Conclusion: This meta-analysis suggests that physical exercise leads to reduction of tumor size in rodents. Since \"maximum daily exercise\" was found to have at least modest impact on tumor growth, more clinical trials investigating dose-response relationships are needed.

The battle against cancer has intensified in the last decade. New experimental techniques and theoretical models have been been proposed to understand the behavior, growth, and evolution of different types of brain tumors. Unfortunately, for glioblastoma multiforme (GBM), except for methylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter that has some benefit in the local control of tumors using alkylating agents such as temozolomide, to date personalized treatments do not exist. In this article, we present a comprehensive review of different aspects intertwined in the mathematical growth modeling applied to high-grade gliomas. We briefly cover the following fundamental aspects related to the conventional imaging in GBM: defining the tumor regions in GBM, segmentation of the tumor regions using magnetic resonance imaging (MRI) of the brain, response assessment using the neuro-oncology response criteria versus the Macdonald criteria, availability of software for the segmentation of MRI of the brain, mathematical modeling applied to tumor growth, principles of mathematical modeling, factors involved in tumor growth models, mathematical modeling based on imaging data, most common equations used in high-grade glioma growth modeling, integration of mathematical growth models in computer simulators, tumor growth modeling as a part of brain\'s complex system, and challenges in mathematical growth modeling. We conclude by saying that it is the combination of biomedical imaging and mathematical modeling that allows the assembling of clinically relevant models of tumor growth and treatment response; the most appropriate model will depend on the premise and findings of each experiment.

Recently, interest in targeted cancer therapies via metabolic pathways has been renewed with the discovery that many tumors become dependent on glucose uptake during anaerobic glycolysis. Also the inability of ketone bodies metabolization due to various deficiencies in mitochondrial enzymes is the major metabolic changes discovered in malignant cells. Therefore, administration of a ketogenic diet (KD) which is based on high in fat and low in carbohydrates might inhibit tumor growth and provide a rationale for therapeutic strategies. So, we conducted this systematic review to assess the effects of KD on the tumor cells growth and survival time in animal studies. All databases were searched from inception to November 2015. We systematically searched the PubMed, Scopus, Google Scholars, Science Direct and Cochrane Library according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. To assess the quality of included studies we used SYRCLE\'s RoB tool. 268 articles were obtained from databases by primary search. Only 13 studies were eligible according to inclusion criteria. From included studies, 9 articles indicate that KD had a beneficial effect on tumor growth and survival time. Tumor types were included pancreatic, prostate, gastric, colon, brain, neuroblastoma and lung cancers. In conclusions, although studies in this field are rare and inconsistence, recent findings have demonstrated that KD can potentially inhibit the malignant cell growth and increase the survival time. Because of differences physiology between animals and humans, future studies in cancer patients treated with a KD are needed.

Ghrelin is a hormone with multiple physiologic functions, including promotion of growth hormone release, stimulation of appetite and regulation of energy homeostasis. Treatment with ghrelin/ghrelin-receptor agonists is a prospective therapy for disease-related cachexia and malnutrition. In vitro studies have shown high expression of ghrelin in cancer tissue, although its role including its impact in cancer risk and progression has not been established. We performed a systematic literature review to identify peer-reviewed human or animal in vivo original research studies of ghrelin, ghrelin-receptor agonists, or ghrelin genetic variants and the risk, presence, or growth of cancer using structured searches in PubMed database as well as secondary searches of article reference lists, additional reviews and meta-analyses. Overall, 45 (73.8%) of the 61 studies reviewed, including all 11 involving exogenous ghrelin/ghrelin-receptor agonist treatment, reported either a null (no statistically significant difference) or inverse association of ghrelin/ghrelin-receptor agonists or ghrelin genetic variants with cancer risk, presence or growth; 10 (16.7%) studies reported positive associations; and 6 (10.0%) reported both negative or null and positive associations. Differences in serum ghrelin levels in cancer cases vs controls (typically lower) were reported for some but not all cancers. The majority of in vivo studies showed a null or inverse association of ghrelin with risk and progression of most cancers, suggesting that ghrelin/ghrelin-receptor agonist treatment may have a favorable safety profile to use for cancer cachexia. Additional large-scale prospective clinical trials as well as basic bioscientific research are warranted to further evaluate the safety and benefits of ghrelin treatment in patients with cancer.