Search Results (372)

Cancer initiation and early tumour growth are complex processes influenced by multiple cellular and microenvironmental factors. A critical aspect of tumour progression is the dynamic interplay between cancer cells and the extracellular matrix (ECM), which undergoes significant alterations to support malignancy. The loss of cell polarity is an early hallmark of tumour progression, disrupting normal tissue architecture and fostering cancerous transformation. Circumstantially, cancer-associated microRNAs (miRNAs) regulate key oncogenic processes, including ECM remodelling, epithelial-to-mesenchymal transition (EMT), and tumorigenic vascular development, further driving tumour growth. ECM alterations, particularly changes in stiffness and mechanotransduction signals, create a supportive niche for cancer cells, enhancing their survival, proliferation, and invasion. EMT and its subtype, epithelial-to-endothelial transition (EET), contribute to tumour plasticity, promote the generation of cancer stem cells (CSCs), and support tumour vascularisation. Furthermore, processes of vascular development like vasculogenesis and angiogenesis are critical for sustaining early tumour growth, supplying oxygen and nutrients to hypoxic malignant cells within the evolving cancerous microenvironments. This review explores key mechanisms underlying these changes in tumorigenic microenvironments, with an emphasis on their collective role for tumour initiation and early tumour growth. It will further delve into present in vitro modelling strategies developed to closely mimic early cancer pathophysiology. Understanding these processes is crucial for developing targeted therapies aimed at disrupting key cancer-promoting pathways and improving clinical outcomes. Full article

Cancer stem cells (CSCs) are a subpopulation with self-renewal and differentiation capacities believed to be responsible for tumor initiation, progression, and recurrence. These cells exhibit unique metabolic features that contribute to their stemness and survival in hostile tumor microenvironments. Like non-stem cancer cells, CSCs primarily rely on glycolysis for ATP production, akin to the Warburg effect. However, CSCs also show increased dependence on alternative metabolic pathways, such as oxidative phosphorylation (OXPHOS) and fatty acid metabolism, which provide necessary energy and building blocks for self-renewal and therapy resistance. The metabolic plasticity of CSCs enables them to adapt to fluctuating nutrient availability and hypoxic conditions within the tumor. Recent studies highlight the importance of these metabolic shifts in maintaining the CSC phenotype and promoting cancer progression. The CSC model suggests that a small, metabolically adaptable subpopulation drives tumor growth and therapy resistance. CSCs can switch between glycolysis and mitochondrial metabolism, enhancing their survival under stress and dormant states. Targeting CSC metabolism offers a promising therapeutic strategy; however, their adaptability complicates eradication. A multi-targeted approach addressing various metabolic pathways is essential for effective CSC elimination, underscoring the need for further research into specific CSC markers and mechanisms that distinguish their metabolism from normal stem cells for successful therapeutic intervention. Full article

Intratumoral hypoxia is common in any form of malignancy initializing focal necrosis or tumor cell adaptation. Hypoxia inducible factor-1-driven reprogramming favors the loss of tumor cell proliferation (quiescence) and partial cellular reversion, induces stemness and/or mesenchymal-like features in the exposed tumor areas. The characteristic hypoxia-driven tumor cell phenotype is principally directed to reduce energy consumption and to enhance survival, but the gained features also contribute to growth advantage and induce the reorganization of the microenvironment and protective mechanisms against external stress. The hypoxia-induced phenotypic changes are at least in part reflected by conventional morphology in breast carcinoma. Intratumoral variability of classical morphological signs, such as the growth pattern, the histological grade, cell proliferation, necrosis, microcalcification, angiogenesis, and the immune cell infiltration is also related with the co-existence of hypoxic areas. Thus, a deeper understanding of hypoxia-activated mechanisms is required. The current paper aims to summarize the major tissue factors involved in the response to hypoxia and their potential contribution to the breast carcinoma phenotype. Full article

Drug resistance remains a major barrier to effective cancer treatment, contributing to poor patient outcomes. Multifunctional biomaterials integrating electrical and catalytic properties offer a transformative strategy to target diverse resistance mechanisms. This review explores their ability to modulate cellular processes, remodel the tumor microenvironment (TME), and enhance drug delivery. Electrically active biomaterials enhance drug uptake and apoptotic sensitivity by altering membrane potentials, ion channels, and intracellular signaling, synergizing with chemotherapy. Catalytic biomaterials generate reactive oxygen species (ROS), activate prodrugs, reprogram hypoxic and acidic TME, and degrade the extracellular matrix (ECM) to improve drug penetration. Hybrid nanomaterials (e.g., conductive hydrogels, electrocatalytic nanoparticles), synergize electrical and catalytic properties for localized, stimuli-responsive therapy and targeted drug release, minimizing systemic toxicity. Despite challenges in biocompatibility and scalability, future integration with immunotherapy, personalized medicine, and intelligent self-adaptive systems capable of real-time tumor response promises to accelerate clinical translation. The development of these adaptive biomaterials, alongside advancements in nanotechnology and AI-driven platforms, represents the next frontier in precision oncology. This review highlights the potential of multifunctional biomaterials to revolutionize cancer therapy by addressing multidrug resistance at cellular, genetic, and microenvironmental levels, offering a roadmap to improve therapeutic outcomes and reshape oncology practice. Full article

Reactive oxygen species (ROS) play a dual role in cancer progression, acting as both signaling molecules and drivers of oxidative damage. Emerging evidence highlights the intricate interplay between ROS, microRNAs (miRNAs), and exosomes within the tumor microenvironment (TME), forming a regulatory axis that modulates immune responses, angiogenesis, and therapeutic resistance. In particular, oxidative stress not only stimulates exosome biogenesis but also influences the selective packaging of redox-sensitive miRNAs (miR-21, miR-155, and miR-210) via RNA-binding proteins such as hnRNPA2B1 and SYNCRIP. These miRNAs, delivered through exosomes, alter gene expression in recipient cells and promote tumor-supportive phenotypes such as M2 macrophage polarization, CD8⁺ T-cell suppression, and endothelial remodeling. This review systematically explores how this ROS–miRNA–exosome axis orchestrates communication across immune and stromal cell populations under hypoxic and inflammatory conditions. Particular emphasis is placed on the role of NADPH oxidases, hypoxia-inducible factors, and autophagy-related mechanisms in regulating exosomal output. In addition, we analyze the therapeutic relevance of natural products and herbal compounds—such as curcumin, resveratrol, and ginsenosides—which have demonstrated promising capabilities to modulate ROS levels, miRNA expression, and exosome dynamics. We further discuss the clinical potential of leveraging this axis for cancer therapy, including strategies involving mesenchymal stem cell-derived exosomes, ferroptosis regulation, and miRNA-based immune modulation. Incorporating insights from spatial transcriptomics and single-cell analysis, this review provides a mechanistic foundation for the development of exosome-centered, redox-modulating therapeutics. Ultimately, this work aims to guide future research and drug discovery efforts toward integrating herbal medicine and redox biology in the fight against cancer. Full article

Glioblastoma (GBM) is an exceedingly aggressive primary brain tumor defined by rapid growth, extensive infiltration, and resistance to standard therapies. A central factor driving these malignancies is the subpopulation of glioblastoma stem cells (GSCs), which possess self-renewal capacity, multipotency, and the ability to regenerate tumor heterogeneity. GSCs contribute to key hallmarks of GBM pathobiology, including relentless progression, resistance to chemotherapy and radiotherapy, and inevitable recurrence. GSCs exhibit distinct molecular signatures, enhanced DNA repair, and metabolic adaptations that protect them against conventional treatments. Moreover, they reside within specialized niches—such as perivascular or hypoxic microenvironments—that sustain stemness, promote immunosuppression, and facilitate angiogenesis. Recent discoveries highlight signaling pathways like Notch, Wnt/β-catenin, Hedgehog, STAT3-PARN, and factors such as TFPI2 and HML-2 as critical regulators of GSC maintenance, plasticity, and immune evasion. These findings underscore the complexity of GSC biology and their pivotal role in driving GBM heterogeneity and therapeutic failure. Emerging therapeutic strategies aim to target GSCs through multiple avenues, including surface markers, immunotherapeutics (e.g., CAR T cells), metabolic vulnerabilities, and combination regimens. Advances in patient-derived organoids, single-cell omics, and 3D co-culture models enable more accurate representation of the tumor ecosystem and personalized therapeutic approaches. Ultimately, improved understanding of GSC-specific targets and the tumor microenvironment promises more effective interventions, paving the way toward better clinical outcomes for GBM patients. Full article

Hypoxic tumors pose considerable obstacles to cancer treatment, as diminished oxygen levels can impair drug effectiveness and heighten therapeutic resistance. Oral cancer, a prevalent malignancy, encounters specific challenges owing to its intricate anatomical structure and the technical difficulties in achieving complete resection, thereby often restricting treatment efficacy. The impact of hypoxia is particularly critical in influencing both the treatment response and prognosis of oral cancers. This article summarizes and examines the potential of polymer nanomedicines to address these challenges. By engineering nanomedicines that specifically react to the hypoxic tumor microenvironment, these pharmaceuticals can markedly enhance targeting precision and therapeutic effectiveness. Polymer nanomedicines enhance therapeutic efficacy while reducing side effects by hypoxia-targeted accumulation. The article emphasizes that these nanomedicines can overcome the drug resistance frequently observed in hypoxic tumors by improving the delivery and bioavailability of anticancer agents. Furthermore, this review elucidates the design and application of polymer nanomedicines for treating hypoxic tumors, highlighting their transformative potential in cancer therapy. Finally, this article gives an outlook on stimuli-responsive polymeric nanomedicines in the treatment of oral cancer. Full article

Glioblastoma (GBM) is a highly aggressive and malignant brain tumor, characterized by hypoxia in its microenvironment, which drives its growth and resistance to treatments. Hypoxia-inducible factor 1 (HIF-1) plays a central role in GBM progression by regulating cellular adaptation to low oxygen availability, promoting processes such as angiogenesis and cell invasion. However, studying and modeling GBM under hypoxic conditions is complex, especially due to the limitations of animal models. In this study, we developed a glioma spheroid model using an alginate–gelatin hydrogel scaffold, which enabled the simulation of hypoxic conditions within the tumor. The scaffold-based model demonstrated high reproducibility, facilitating the analysis of HIF-1α expression, a key protein in the hypoxic response of GBM. Furthermore, cell viability, the microstructural features of the encapsulated spheroids, and the water absorption rate of the hydrogel were assessed. Our findings validate the three-dimensional (3D) glioblastoma spheroids model as a valuable platform for studying hypoxia in GBM and evaluating new therapies. This approach could offer a more accessible and specific alternative for studying the tumor microenvironment and therapeutic resistance in GBM. Full article

In this study, we developed a novel theranostic nanomedicine formulation that integrates multimodal imaging with controlled drug release in reactive oxygen species (ROS)-rich microenvironments. A fluorinated oxalate compound (FOC) was synthesized through a one-step condensation reaction between 1,1,1,3,3,3-hexafluoro-2-propanol and oxalyl chloride, characterized by ¹H, ¹³C, and ¹⁹F NMR spectroscopy. The FOC and luminophore-incorporated nanomedicine formulations reacted rapidly with hydrogen peroxide via the peroxyoxalate chemiluminescence (POCL) mechanism, producing strong chemiluminescence and inducing a notable 19-fold increase in ratiometric ¹⁹F NMR signal upon conversion to fluorinated alcohol (FAH), demonstrating promising potential for high-contrast ¹⁹F MRI in deep tissue. Following ROS stimulation, the chemical conversion from hydrophobic FOC to hydrophilic FAH led to the degradation of the nanomedicines, facilitating payload release. In vitro experiments with A-431 cancer cells under hypoxic conditions confirmed ROS-responsive drug release, evidenced by enhanced fluorescence from model luminophores. Additionally, doxorubicin-loaded FOC nanomedicines reduced cell viability to 32% under hypoxia while remaining non-toxic in normoxic conditions. These results indicate that FOC-based nanomedicine formulations provide a promising platform for combined chemiluminescence and ¹⁹F MRI with targeted therapeutic efficacy in ROS-rich inflammatory and cancerous tissues. Full article

Hypoxia-inducible factor-1α (HIF-1α), a master regulator of cellular adaptation to hypoxia, drives colorectal cancer (CRC) progression by fueling angiogenesis, metastasis, and therapy resistance. Emerging evidence delineates intricate crosstalk between non-coding RNAs (ncRNAs)—including microRNAs, long non-coding RNAs, and circular RNAs—and HIF-1α, forming bidirectional regulatory networks that orchestrate CRC pathogenesis. By interacting with HIF-1α, these non-coding RNAs contribute to the orchestration of the aggressive hypoxic tumor microenvironment. Recent studies have evaluated the clinical potential of lncRNAs and miRNAs in the realms of non-invasive liquid biopsies and RNA-targeted therapies. This review offers a comprehensive synthesis of recent investigations into the mechanisms by which lncRNAs and miRNAs interact with HIF-1α to modulate CRC progression. Additionally, we further explore the clinical implications of ncRNA/HIF-1α crosstalk, emphasizing their potential as diagnostic biomarkers and therapeutic targets, while also spotlighting intriguing and promising areas of ncRNA research. Methods: In this study, our search strategy employed in databases such as PubMed, Web of Science, and EMBASE is as follows: we will specify search terms, including combinations of “non-coding RNA”, “HIF-1α”, and “colorectal cancer”, along with a date range for the literature search (for example, from 2000 to 2025) to capture the most relevant and up-to-date research. Full article

Impeded by the limited light penetration of photodynamic therapy (PDT) to tissues and the hypoxic environment of solid tumors, the clinical therapeutic efficacy and application are below expectations. In this study, a glutathione (GSH)-responsive nano-photosensitizer, based on the chlorquinaldol (CQD)-loaded iron-containing nanorod composed of meso-tetra (4-carboxyphenyl) porphyrin (TCPP), was prepared to serve as the laser-ignited ferroptosis sensitizer to improve the tumoricidal effect of PDT. In the tumor microenvironment (TME) with elevated GSH levels, therapeutic cargos and ferrous ions are released and are accompanied by the degradation of the nano-photosensitizer and GSH exhaustion. This not only increases liable iron pool (LIP) accumulation by the released ferrous ions but also decreases glutathione peroxidase 4 (GPX4) activity by GSH exhaustion. Simultaneously, GSH exhaustion disrupts intracellular redox homeostasis, heightening NIR light irradiation-triggered photosensitive oxidative stress. Moreover, the released CQD elevates the level of intracellular reactive oxygen species (ROS), enabling the nanorods to gain an oxygen radical generation ability and enhancing the photosensitive oxidative therapeutic efficacy. Strikingly, CQD exacerbates the downregulation of GPX4 expression to promote the accumulation of lipid peroxides. Therefore, we herald a new paradigm for synergistically potentiating PDT based on the “all-in-one” nano-photosensitizer through the multi-pronged upregulation of ferroptosis sensitivity. Full article

Photodynamic therapy (PDT) is an innovative treatment that has recently been approved for clinical use and holds promise for cancer patients. It offers several benefits, such as low systemic toxicity, minimal invasiveness, and the ability to stimulate antitumor immune responses. For certain types of cancer, it has shown positive results with few side effects. However, PDT still faces some challenges, including limited light penetration into deeper tumor tissues, uneven distribution of the photosensitizer (PS) that can also affect healthy cells, and the difficulties posed by the hypoxic tumor microenvironment (TME). In hypoxic conditions, PDT’s effectiveness is reduced due to insufficient production of reactive oxygen species, which limits tumor destruction and can lead to relapse. This review highlights recent advances in photosensitizers and nanotechnologies that are being developed to improve PDT. It focuses on multifunctional nanoplatforms and nanoshuttles that have shown promise in preclinical studies, especially for treating solid tumors. One of the key areas of focus is the development of PSs that specifically target mitochondria to treat deep-seated malignant tumors. New mitochondria-targeting nano-PSs are designed with better water solubility and extended wavelength ranges, allowing them to target tumors more effectively, even in challenging, hypoxic environments. These advancements in PDT are opening new doors for cancer treatment, especially when combined with other therapeutic strategies. Moving forward, research should focus on optimizing PDT, creating more efficient drug delivery systems, and developing smarter PDT platforms. Ultimately, these efforts aim to make PDT a first-choice treatment option for cancer patients. Full article

Perirenal adipose tissue (PRAT) exhibits particular morphological features, with its activity being mainly related to thermogenesis. However, an expanded PRAT area seems to play a significant role in cardiovascular diseases, diabetes mellitus, and chronic kidney disease pathogenesis. Numerous studies have demonstrated that PRAT may support cancer progression and invasion, mainly in obese patients. The mechanism underlying these processes is of dysregulation of PRAT’s secretion of adipokines and pro-inflammatory cytokines, such as leptin, adiponectin, chemerin, apelin, omentin-1, vistatin, nesfatin-1, and other pro-inflammatory cytokines, modulated by tumor cells. Cancer cells may also induce a metabolic reprogramming of perirenal adipocytes, leading to increased lipids and lactate transfer to the tumor microenvironment, contributing to cancer growth in a hypoxic milieu. In addition, the PRAT browning process has been specifically detected in renal cell carcinoma (RCC), being characterized by upregulated expression of brown/beige adipocytes markers (UCP1, PPAR-ɣ, c/EBPα, and PGC1α) and downregulated white fat cells markers, such as LEPTIN, SHOX2, HOXC8, and HOXC9. Considering its multifaceted role in cancer, modulation of PRAT’s role in tumor progression may open new directions for oncologic therapy improvement. Considering the increasing evidence of the relationship between PRAT and tumor cells, our review aims to provide a comprehensive analysis of the perirenal adipocytes’ impact on tumor progression and metastasis. Full article

Despite ongoing advancements, cancer remains a significant global health concern, with a persistent challenge in identifying a definitive cure. While various cancer therapies have been developed and approved, offering treatments for smaller neoplasms, their efficacy diminishes in solid tumors and hypoxic environments, particularly for chemotherapy and radiation therapy. A novel approach, Clostridium-based therapy, has emerged as a promising candidate for current solid tumor treatments due to its unique affinity for the hypoxic tumor microenvironment. This review examines the potential of Clostridium in cancer treatment, encompassing direct tumor lysis, immune modulation, and synergistic effects with existing cancer therapies. Advancements in synthetic biology have further enhanced its potential through genetic modifications, such as the removal of alpha toxin gene from Clostridium novyi-NT, the implementation of targeted approaches, and reduction in systemic toxicity. Although preclinical and clinical studies have demonstrated that Clostridium-based treatments combined with other therapies hold promise for complete cancer eradication, challenges persist. Through this review, we also propose that the integration of various methods and technologies together with Clostridium-based therapy may lead to the complete eradication of cancer in the future. Full article

Hypoxia-Inducible Factor-1α (HIF-1α) is crucial in the progression of ovarian cancer, especially in influencing its tumor microenvironment and promoting pathogenic pathways that worsen female infertility. In hypoxic settings, HIF-1α is stabilized and activates the transcription of genes associated with angiogenesis, metabolic reprogramming, epithelial-to-mesenchymal transition, and therapeutic resistance. Angiogenesis and glycolytic reprogramming mediated by HIF-1 tumor proliferation, survival, and metastasis. Its dysfunction concurrently impairs ovarian homeostasis, undermining follicular growth, hormone synthesis, and the ovarian vascular network, consequently contributing to infertility. Moreover, HIF-1α induces persistent inflammation and oxidative stress, promoting an environment damaging to reproductive health. Due to its dual function in ovarian cancer growth and infertility, HIF-1α is a potential therapeutic target. Strategies including small molecule inhibitors and nanoparticle-mediated delivery of drugs possess the potential to reduce HIF-1α activity, hence reducing cancer progression while protecting fertility. This review seeks to clarify the molecular basis of HIF-1α in ovarian cancer and its effects on female infertility, providing insights into novel treatment approaches that target both controlling the disease and preserving fertility. Full article