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BACKGROUND: Previous graduate students and postdoctoral associates from the University of Florida Health Cancer Center, in partnership with the University of Florida Student Science Training Program, implemented a cooperative learning curriculum, providing high school students with a broad overview of cancer topics over six weeks over the summer. To address discussions necessitated by the COVID-19 pandemic on student autonomy, we report lessons learned and outcomes of a cancer biology and therapeutic curriculum modified for a collaborative learning environment. METHODS: This pre-post longitudinal observational study conducted in 2023 on a cancer biology and therapeutics course evaluated students' knowledge retention and general awareness and opinions in cancer research. A structured survey was employed for data collection, using learning assessment surveys and the Likert scale ranging from 1 to 10, with 10 being highly likely. RESULTS: Student performance tracked over a 7-year period indicated consistency in performance between years. Post-assessment analysis revealed significant improvements in student benchmark understanding, notably in their ability to define cancer in one sentence (p = 0.0407), identify cancer therapies (p = 0.0040), and recognize cancer hallmarks (p < 0.0001). An increased trend in median response to the likelihood of pursuing cancer research (p = 0.8793) and the possibility of pursuing cancer research (p = 0.4874) were also observed, although not statistically significant. Moreover, feedback from participating students indicated that "the educational activities at the end of class (e.g., escape room, case studies)" and "learning about cancer and getting to work in groups…" the curriculum fostered a positive educational learning environment. CONCLUSION: Students generally retained the course material presented and upheld a positive perception of the course. Incorporating opportunities for peer-to-peer learning, especially when introducing or discussing complex issues like cancer, may benefit student autotomy.

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Cancer continues to be a prominent issue in healthcare systems, resulting in approximately 9.9 million fatalities in 2020. It is the second most common cause of death after cardiovascular diseases. Although there are difficulties in treating cancer at both the genetic and phenotypic levels, many cancer patients seek supplementary and alternative medicines to cope with their illness, relieve symptoms, and reduce the side effects of cytotoxic drug therapy. Consequently, there is an increasing emphasis on studying natural products that have the potential to prevent or treat cancer. Cancer cells depend on multiple hallmarks to secure survival. These hallmarks include sustained proliferation, apoptosis inactivation, stimulation of angiogenesis, immune evasion, and altered metabolism. Several natural products from food were reported to target multiple cancer hallmarks and can be used as adjuvant interventions to augment conventional therapies. This review summarizes the main active ingredients in food that have anticancer activities with a comprehensive discussion of the mechanisms of action. Thymoquinone, allicin, resveratrol, parthenolide, Epigallocatechin gallate, and piperine are promising anticancer bioactive ingredients in food. Natural products discussed in this review provide a solid ground for researchers to provide effective anticancer functional food.

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PIWI-interacting RNAs (piRNAs) have received a lot of attention for their functions in cancer research. This class of short non-coding RNAs (ncRNA) has roles in genomic stability, chromatin remodeling, messenger RNA (mRNA) integrity, and genome structure. We summarized the mechanisms underlying the biogenesis and regulatory molecular functions of piRNAs. Among all piRNAs studied in cancer, this review offers a comprehensive analysis of the emerging roles of piR-823 in various types of cancer, including colorectal, gastric, liver, breast, and renal cancers, as well as multiple myeloma. piR-823 has emerged as a crucial modulator of various cancer hallmarks through regulating multiple pathways. In the current review, we analyzed several databases and conducted an extensive literature search to explore the influence of piR-823 in carcinogenesis in addition to describing the potential application of piR-823 as prognostic and diagnostic markers as well as the therapeutic potential toward ncRNA precision.

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In this review, we consider the role of cell-cell fusion in cancer development and progression through an evolutionary lens. We begin by summarizing the origins of fusion proteins (fusogens), of which there are many distinct classes that have evolved through convergent evolution. We then use an evolutionary framework to highlight how the persistence of fusion over generations and across different organisms can be attributed to traits that increase fitness secondary to fusion; these traits map well to the expanded hallmarks of cancer. By studying the tumor microenvironment, we can begin to identify the key selective pressures that may favor higher rates of fusion compared to healthy tissues. The paper concludes by discussing the increasing number of research questions surrounding fusion, recommendations for how to answer them, and the need for a greater interest in exploring cell fusion and evolutionary principles in oncology moving forward.

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Circular RNAs (circRNAs) represent a distinct class of covalently closed RNA species lacking conventional 5' to 3' polarity. Derived predominantly from pre-mRNA transcripts of protein-coding genes, circRNAs arise through back-splicing events of exon-exon or exon-intron junctions. They exhibit tissue- and cell-specific expression patterns and play crucial roles in regulating fundamental cellular processes such as cell cycle dynamics, proliferation, apoptosis, and differentiation. CircRNAs modulate gene expression through a plethora of mechanisms at epigenetic, transcriptional, and post-transcriptional levels, and some can even undergo translation into functional proteins. Recently, aberrant expression of circRNAs has emerged as a significant molecular aberration within the intricate regulatory networks governing hallmarks of cancer. The tumor-specific expression patterns and remarkable stability of circRNAs have profound implications for cancer diagnosis, prognosis, and therapy. This review comprehensively explores the multifaceted roles of circRNAs across cancer hallmarks in various tumor types, underscoring their growing significance in cancer diagnosis and therapeutic interventions. It also details strategies for leveraging circRNA-based therapies and discusses the challenges in using circRNAs for cancer management, emphasizing the need for further research to overcome these obstacles.

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Colorectal cancer (CRC) presents ongoing challenges due to limited treatment effectiveness and a discouraging prognosis, underscoring the need for ground-breaking therapeutic approaches. This review delves into the pivotal role of E3 ubiquitin ligases and deubiquitinases (DUBs), underscoring their role as crucial regulators for tumor suppression and oncogenesis in CRC. We spotlight the diverse impact of E3 ligases and DUBs on CRC's biological processes and their remarkable versatility. We closely examine their specific influence on vital signaling pathways, particularly Wnt/ß-catenin and NF-κB. Understanding these regulatory mechanisms is crucial for unravelling the complexities of CRC progression. Importantly, we explore the untapped potential of E3 ligases and DUBs as novel CRC treatment targets, discussing aspects that may guide more effective therapeutic strategies. In conclusion, our concise review illuminates the E3 ubiquitin ligases and deubiquitinases pivotal role in CRC, offering insights to inspire innovative approaches for transforming the treatment landscape in CRC.

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Mixed-lineage kinase 3 (MLK3) is a serine/threonine kinase of the MAPK Kinase kinase (MAP3K) family that plays critical roles in various biological processes, including cancer. Upon activation, MLK3 differentially activates downstream MAPKs, such as JNK, p38, and ERK. In addition, it regulates various non-canonical signaling pathways, such as ß-catenin, AMPK, Pin1, and PAK1, to regulate cell proliferation, apoptosis, invasion, and metastasis. Recent studies have also uncovered other potentially diverse roles of MLK3 in malignancy, which include metabolic reprogramming, cancer-associated inflammation, and evasion of cancer-related immune surveillance. The role of MLK3 in cancer is complex and cancer-specific, and an understanding of its function at the molecular level aligned specifically with the cancer hallmarks will have profound therapeutic implications for diagnosing and treating MLK3-dependent cancers. This review summarizes the current knowledge about the effect of MLK3 on the hallmarks of cancer, providing insights into its potential as a promising anticancer drug target.

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Ubiquitination, a pivotal posttranslational modification of proteins, plays a fundamental role in regulating protein stability. The dysregulation of ubiquitinating and deubiquitinating enzymes is a common feature in various cancers, underscoring the imperative to investigate ubiquitin ligases and deubiquitinases (DUBs) for insights into oncogenic processes and the development of therapeutic interventions. In this review, we discuss the contributions of the ubiquitin-proteasome system (UPS) in all hallmarks of cancer and progress in drug discovery. We delve into the multiple functions of the UPS in oncology, including its regulation of multiple cancer-associated pathways, its role in metabolic reprogramming, its engagement with tumor immune responses, its function in phenotypic plasticity and polymorphic microbiomes, and other essential cellular functions. Furthermore, we provide a comprehensive overview of novel anticancer strategies that leverage the UPS, including the development and application of proteolysis targeting chimeras (PROTACs) and molecular glues.

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Protein SUMOylation, a post-translational modification, intricately regulates diverse biological processes including gene expression, cell cycle progression, signaling pathway transduction, DNA damage response, and RNA metabolism. This modification contributes to the acquisition of tumorigenicity and the maintenance of cancer hallmarks. In malignancies, protein SUMOylation is triggered by various cellular stresses, promoting tumor initiation and progression. This augmentation is orchestrated through its specific regulatory mechanisms and characteristic biological functions. This review focuses on elucidating the fundamental regulatory mechanisms and pathological functions of the SUMO pathway in tumor pathogenesis and malignant evolution, with particular emphasis on the tumorigenic potential of SUMOylation. Furthermore, we underscore the potential therapeutic benefits of targeting the SUMO pathway, paving the way for innovative anti-tumor strategies by perturbing this dynamic and reversible modifying process.

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Cancer is a profoundly dynamic, heterogeneous and aggressive systemic ailment, with a coordinated evolution of various types of tumor niches. Hypoxia plays an indispensable role in the tumor micro-ecosystem, drastically enhancing the plasticity of cancer cells, fibroblasts and immune cells and orchestrating intercellular communication. Hypoxia-induced signals, particularly hypoxia-inducible factor-1α (HIF-1α), drive the reprogramming of genetic, transcriptional, and proteomic profiles. This leads to a spectrum of interconnected processes, including augmented survival of cancer cells, evasion of immune surveillance, metabolic reprogramming, remodeling of the extracellular matrix, and the development of resistance to conventional therapeutic modalities like radiotherapy and chemotherapy. Here, we summarize the latest research on the multifaceted effects of hypoxia, where a multitude of cellular and non-cellular elements crosstalk with each other and co-evolve in a synergistic manner. Additionally, we investigate therapeutic approaches targeting hypoxic niche, encompassing hypoxia-activated prodrugs, HIF inhibitors, nanomedicines, and combination therapies. Finally, we discuss some of the issues to be addressed and highlight the potential of emerging technologies in the treatment of cancer.

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BACKGROUND: Carcinogenesis is driven by interactions between genetic mutations and the local tumor microenvironment. Recent research has identified hundreds of cancer driver genes; however, these studies often include a mixture of different molecular subtypes and ecological niches and ignore the impact of the immune system. RESULTS: In this study, we compare the landscape of driver genes in tumors that escaped the immune system (escape +) versus those that did not (escape -). We analyze 9896 primary tumors from The Cancer Genome Atlas using the ratio of non-synonymous to synonymous mutations (dN/dS) and find 85 driver genes, including 27 and 16 novel genes, in escape - and escape + tumors, respectively. The dN/dS of driver genes in immune escaped tumors is significantly lower and closer to neutrality than in non-escaped tumors, suggesting selection buffering in driver genes fueled by immune escape. Additionally, we find that immune evasion leads to more mutated sites, a diverse array of mutational signatures and is linked to tumor prognosis. CONCLUSIONS: Our findings highlight the need for improved patient stratification to identify new therapeutic targets for cancer treatment.

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The present study explores the complex roles of High Mobility Group Box 1 (HMGB1) in the context of cancer development, emphasizing glioblastoma (GBM) and other central nervous system (CNS) cancers. HMGB1, primarily known for its involvement in inflammation and angiogenesis, emerges as a multifaceted player in the tumorigenesis of GBM. The overexpression of HMGB1 correlates with glioma malignancy, influencing key pathways like RAGE/MEK/ERK and RAGE/Rac1. Additionally, HMGB1 secretion is linked to the maintenance of glioma stem cells (GSCs) and contributes to the tumor microenvironment's (TME) vascular leakiness. Henceforth, our review discusses the bidirectional impact of HMGB1, acting as both a promoter of tumor progression and a mediator of anti-tumor immune responses. Notably, HMGB1 exhibits tumor-suppressive roles by inducing apoptosis, limiting cellular proliferation, and enhancing the sensitivity of GBM to therapeutic interventions. This dualistic nature of HMGB1 calls for a nuanced understanding of its implications in GBM pathogenesis, offering potential avenues for more effective and personalized treatment strategies. The findings underscore the need to explore HMGB1 as a prognostic marker, therapeutic target, and a promising tool for stimulating anti-tumor immunity in GBM.

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The nuclear factor-κB (NF-κB) family, consisting of several transcription factors, has been implicated in the regulation of cell proliferation and invasion, as well as inflammatory reactions and tumor development. Cervical cancer (CC) results from long-term interactions of multiple factors, among which persistent high-risk human papillomavirus (hrHPV) infection is necessary. During different stages from early to late after HPV infection, the activity of NF-κB varies and plays various roles in carcinogenesis and progress of CC. As the center of the cell signaling transduction network, NF-κB can be activated through classical and non-classical pathways, and regulate the expression of downstream target genes involved in regulating the tumor microenvironment and acquiring hallmark traits of CC cells. Targeting NF-κB may help treat CC and overcome the resistance to radiation and chemotherapy. Even though NF-κB inhibitors have not been applied in clinical treatment as yet, due to limitations such as dose-restrictive toxicity and poor tumor-specificity, it is still considered to have significant therapeutic potential and application prospects. In this review, we focus on the role of NF-κB in the process of CC occurrence and hallmark capabilities acquisition. Finally, we summarize relevant NF-κB-targeted treatments, providing ideas for the prevention and treatment of CC.

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The concept of 'Hallmarks of Cancer' is an approach of reducing the enormous complexity of cancer to a set of guiding principles. As the underlying mechanism of cancer are portrayed, we find that we gain insight and additional aspects of the disease arise. The understanding of the tumor microenvironment (TME) brought a new dimension and led to the discovery of novel hallmarks such as senescent cells, non-mutational epigenetic reprogramming, polymorphic microbiomes and unlocked phenotypic plasticity. Circular RNAs (circRNAs) are single-stranded, covalently closed RNA molecules that are ubiquitous across all species. Recent studies on the circRNAs have highlighted their crucial function in regulating the formation of human malignancies through a range of biological processes. The primary goal of this review is to clarify the role of circRNAs in the most common form of liver cancer, hepatocellular carcinoma (HCC). This review also addressed the topic of how circRNAs affect HCC hallmarks, including the new generation hallmarks. Finally, the enormous applications that these rapidly expanding ncRNA molecules serve in the functional and molecular development of effective HCC diagnostic biomarkers and therapeutic targets.

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Natural products, particularly medicinal plants, are crucial in combating cancer and aiding in the discovery and development of new therapeutic agents owing to their biologically active compounds. They offer a promising avenue for developing effective anticancer medications because of their low toxicity, diverse chemical structures, and ability to target various cancers. Allicin is one of the main ingredients in garlic (Allium sativum L.). It is a bioactive sulfur compound maintained in various plant sections in a precursor state. Numerous studies have documented the positive health benefits of this natural compound on many chronic conditions, including gastric, hepatic, breast, lung, cervical, prostate, and colon cancer. Moreover, allicin may target several cancer hallmarks or fundamental biological traits and functions that influence cancer development and spread. Cancer hallmarks include sustained proliferation, evasion of growth suppressors, metastasis, replicative immortality, angiogenesis, resistance to cell death, altered cellular energetics, and immune evasion. The findings of this review should provide researchers and medical professionals with a solid basis to support fundamental and clinical investigations of allicin as a prospective anticancer drug. This review outlines the anticancer role of allicin in each hallmark of cancer.

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Epigallocatechin gallate (EGCG) is a catechin, which is a type of flavonoid found in high concentrations in green tea. EGCG has been studied extensively for its potential health benefits, particularly in cancer. EGCG has been found to exhibit anti-proliferative, anti-angiogenic, and pro-apoptotic effects in numerous cancer cell lines and animal models. EGCG has demonstrated the ability to interrupt various signaling pathways associated with cellular proliferation and division in different cancer types. EGCG anticancer activity is mediated by interfering with various cancer hallmarks. This article summarize and highlight the effects of EGCG on cancer hallmarks and focused on the impacts of EGCG on these cancer-related hallmarks. The studies discussed in this review enrich the understanding of EGCG's potential as a therapeutic tool against cancer, offering a substantial foundation for scientists and medical experts to advance scientific and clinical investigations regarding EGCG's possibility as a potential anticancer treatment.

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BACKGROUND: Disrupted protein homeostasis (proteostasis) has been demonstrated to facilitate the progression of various diseases. The cytosolic T-complex protein-1 ring complex (TRiC/CCT) was discovered to be a critical player in orchestrating proteostasis by folding eukaryotic proteins, guiding intracellular localisation and suppressing protein aggregation. Intensive investigations of TRiC/CCT in different fields have improved the understanding of its role and molecular mechanism in multiple physiological and pathological processes. MAIN BODY: In this review, we embark on a journey through the dynamic protein folding cycle of TRiC/CCT, unraveling the intricate mechanisms of its substrate selection, recognition, and intriguing folding and assembly processes. In addition to discussing the critical role of TRiC/CCT in maintaining proteostasis, we detail its involvement in cell cycle regulation, apoptosis, autophagy, metabolic control, adaptive immunity and signal transduction processes. Furthermore, we meticulously catalogue a compendium of TRiC-associated diseases, such as neuropathies, cardiovascular diseases and various malignancies. Specifically, we report the roles and molecular mechanisms of TRiC/CCT in regulating cancer formation and progression. Finally, we discuss unresolved issues in TRiC/CCT research, highlighting the efforts required for translation to clinical applications, such as diagnosis and treatment. CONCLUSION: This review aims to provide a comprehensive view of TRiC/CCT for researchers to inspire further investigations and explorations of potential translational possibilities.

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The conventional computational approaches to investigating a disease confront inherent constraints as they often need to improve in delving beyond protein functional associations and grasping their deeper contextual significance within the disease framework. Such context-specificity can be explored using clinical data by evaluating the change in interaction between the biological entities in different conditions by investigating the differential co-expression relationships. We believe that the integration and analysis of differential co-expression and the functional relationships, primarily focusing on the source nodes, will open novel insights about disease progression as the source proteins could trigger signaling cascades, mostly because they are transcription factors, cell surface receptors, or enzymes that respond instantly to a particular stimulus. A thorough contextual investigation of these nodes could lead to a helpful beginning point for identifying potential causal linkages and guiding subsequent scientific investigations to uncover mechanisms underlying observed associations. Our methodology includes functional protein-protein Interaction (PPI) data and co-expression information and filters functional linkages through a series of critical steps, culminating in the identification of a robust set of regulators. Our analysis identified eleven key regulators-AKT1, BRCA1, CAMK2G, CUL1, FGFR3, KIF3A, NUP210, PRKACB, RAB8A, RPS6KA2 and TGFB3-in glioblastoma. These regulators play a pivotal role in disease classification, cell growth control, and patient survivability and exhibit associations with immune infiltrations and disease hallmarks. This underscores the importance of assessing correlation towards causality in unraveling complex biological insights.

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Follistatin (FST) is a potent neutralizer of the transforming growth factor-ß superfamily and is associated with normal cellular programs and various hallmarks of cancer, such as proliferation, migration, angiogenesis, and immune evasion. The aberrant expression of FST by solid tumors is a well-documented observation, yet how FST influences tumor progression and therapy response remains unclear. The recent surge in omics data has revealed new insights into the molecular foundation underpinning tumor heterogeneity and its microenvironment, offering novel precision medicine-based opportunities to combat cancer. In this review, we discuss these recent FST-centric studies, thereby offering an updated perspective on the protean role of FST isoforms in shaping the complex cellular ecosystem of tumors and in mediating drug resistance.

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In recent years, accumulating evidence from preclinical and clinical studies consistently indicated that physical activity/exercise plays a crucial role in reducing the incidence and recurrence of various malignancies, by exerting a beneficial modulation of cancer hallmarks. Moreover, physical activity is suggested to attenuate certain adverse effects of anticancer therapy, including the reduction of cardiovascular toxicity and symptoms related to depression and anxiety, among others, while preserving muscular strength. In the case of melanoma, the relationship with physical activity has been critically debated. Historically, several cohort studies and meta-analyses reported a positive association between physical activity/exercise and melanoma risk. This association was primarily attributed to outdoor activities that may expose the skin to UV radiation, a well-known risk factor for melanocyte transformation. However, more recent evidence does not support such association and recognizes physical activity/exercise role in both melanoma prevention and progression. Nevertheless, sun protection is recommended during outdoor training to minimize UV radiation exposure. This narrative review summarizes preclinical and clinical data about physical activity effects on melanoma hallmarks. Specifically, experimental evidence is reported concerning (i) invasion and metastasis, (ii) reprogramming of energy metabolism, (iii) angiogenesis, (iv) resistance to cell death, (v) evasion from immune destruction, and (vi) tumor-promoting inflammation.