搜索结果：Seminars in cancer biology

Clear cell renal cell carcinoma (ccRCC) exhibits a distinctive metabolic signature marked by the excessive buildup of cholesterol and neutral lipids. This phenotype stems largely from the loss of the von Hippel-Lindau (VHL) tumor suppressor and the resulting stabilization of hypoxia-inducible factors (HIFs). The altered lipid environment enables ccRCC cells to sustain growth, evade immune surveillance, and withstand contemporary systemic therapies. Increasing evidence indicates that similar disturbances in lipid metabolism contribute to kidney injury during cancer treatment, suggesting that dysregulated cholesterol handling represents a shared pathologic foundation linking tumor progression with therapy-induced nephrotoxicity. This review brings together mechanistic, preclinical, and translational findings that illuminate how defective cholesterol regulation-particularly diminished ABCA1-mediated efflux promotes tumor aggressiveness while heightening renal vulnerability to radiation therapy, tyrosine kinase inhibitors (TKIs), and immune checkpoint inhibitors (ICIs). We examine lipid droplet dynamics, cholesteryl ester biology, and mitochondrial perturbations in ccRCC cells and renal parenchymal cells exposed to therapeutic stress. Across ccRCC therapies, lipid accumulation drives renal injury, with lipid-sensitive cells, particularly podocytes, undergoing cytoskeletal and slit-diaphragm disruption, proteinuria, and progressive glomerular damage in response to cholesterol overload, oxidative stress, and inflammatory signaling. Within the tumor, suppression of ABCA1 perpetuates lipid droplet expansion, reinforces resistance to therapy, and intensifies metabolic strain within the microenvironment. Restoring cholesterol balance through LXR agonists, cyclodextrins, or strategies that enhance ABCA1 function holds promise for limiting renal toxicity while simultaneously impairing tumor survival mechanisms. Advances in lipidomics, metabolic imaging, and biomarker-driven stratification may facilitate precision approaches that integrate metabolic correction with effective oncologic care.

Cancer is a complex group of diseases characterized by the uncontrolled growth and spread of abnormal cells, and it remains a major global health concern. In order to meet the increased energy and biosynthetic requirements of rapid growth, cancer cells undergo metabolic reprogramming. In this setting, nutrition exerts a crucial influence on nutrients availability and increasing evidence highlights the significant role of nutrition in the prevention, development, and management of cancer. Dietary patterns and nutrient intake can influence cancer risk through various biological mechanisms, including inflammation, oxidative stress, immune modulation, and hormonal regulation. Diets high in processed foods, red meats, saturated fats and added sugars, have been associated with an increased risk of several cancers. Such diets may contribute to chronic inflammation, insulin resistance, and obesity-conditions known as major risk factors for cancer. Obesity itself is considered a significant contributor to cancer incidence and mortality, linking excess body fat to hormonal imbalances and altered metabolic pathways. Conversely, balanced diets rich in fruits, vegetables, whole grains, legumes, healthy fats and low refined carbohydrates, provide essential vitamins, minerals, fiber, and phytochemicals that have protective properties. These components can help the scavenging of free radicals, reduce DNA damage, and regulate cell growth, potentially lowering the risk of developing certain types of cancer. Nutritional needs in patients with cancer become complex, because of changes in metabolism and tolerance, frequently associated with cancer progression and treatment. Personalized nutritional support can help maintain body weight, preserve muscle mass, and improve treatment tolerance, potentially enhancing overall performance status and survival. While nutrition is not a cure for cancer, it is an essential component of an integrative approach to prevention and care. Further research is necessary to explore how diet can be optimized to support long-term health, reduce recurrence, and improve outcomes in cancer.

Obesity is an established risk factor for at least thirteen cancer types, yet the mechanisms by which the gut microbiota participates in obesity-related tumorigenesis remain incompletely understood. In this review, we summarize the role of the gut microbiota in the four core oncogenic pathways of obesity including metabolic reprogramming, the obesity-related secretome, hormonal dysregulation, and immune modulation. Mechanistically, microbial activity shapes these processes primarily through the production of metabolites, disruption of the intestinal barrier, and stimulation of innate immunity via microbe-associated molecular patterns, ultimately contributing to chronic low-grade inflammation and impaired antitumor immune surveillance. Nevertheless, many outstanding questions remain. Microbial signals are not uniformly tumor-promoting, in obesity- related liver cancer models, short-chain fatty acid-producing taxa can suppress pro-tumor inflammation. In terms of cancer type, the evidence for mechanistic involvement is strongest for colorectal and liver cancers, owing to the gut-liver axis and direct epithelial exposure, whereas causal inferences for other cancer types remain limited. Moreover, the role of intratumoral microbiota remains uncertain due to low microbial biomass and potential sequencing contamination. Key translational challenges include confounding factors such as diet and co-treatments, inconsistencies in obesity phenotyping across studies, and platform-dependent variability in microbial biomarkers. Nonetheless, microbial interventions aimed at targeting obesity-related cancer development and progression represent a promising avenue for future therapeutic strategies.

Oligometastatic and oligoprogressive disease treated with stereotactic ablative radiotherapy (SABR) represents a clinically heterogeneous entity. Increasing evidence suggests that anatomical definitions alone may not adequately capture underlying biological diversity. This systematic review aimed to synthesize translational evidence exploring evolutionary dynamics, resistance mechanisms, and biomarker-driven stratification in patients treated with SABR. A systematic literature review was performed including prospective and retrospective studies evaluating translational biomarkers in oligometastatic or oligoprogressive settings treated with SABR. Studies assessing genomic, transcriptomic, circulating or immune-related biomarkers were included. Data were summarized qualitatively according to predefined translational domains: (i) evolutionary dynamics under systemic therapy pressure, (ii) baseline biological stratification, (iii) longitudinal circulating biomarkers, and (iv) systemic immune remodeling. Exploratory quantitative visual syntheses were performed using reported hazard ratios when conceptually comparable endpoints were available. 19 studies comprising 1,527 patients were included. Across tumor types and treatment contexts, translational analyses consistently indicated that anatomically defined oligometastatic states encompass biologically distinct subgroups with different risks of systemic progression. Studies evaluating oligoprogression under ongoing systemic therapy suggested a distinction between spatially constrained resistance and systemic molecular escape, supported by circulating tumor DNA and tissue- or plasma-based molecular profiling (including genomic and transcriptomic analyses). Baseline biological features, including adverse genomic signatures and circulating biomarkers, were associated with inferior progression outcomes despite metastasis-directed therapy. Longitudinal biomarkers provided early signals of treatment response and systemic control. Immune remodeling after SABR showed context-dependent effects, both systemic immune activation and treatment-related immunosuppression reported across studies.

Obesity-induced chronic inflammation and lipid metabolic imbalance form a pivotal nexus linking cardiovascular disease and cancer. Dysfunctional adipose tissue establishes a pro-inflammatory environment through hypoxia-driven macrophage polarization, oxidative stress, aberrant lipid signaling, and endocrine crosstalk, mechanisms that collectively foster atherogenesis and tumor promotion. Yet, a comprehensive integration of metabolic and immunological dynamics at the molecular level remains elusive. In this review, we synthesize emerging evidence that metabolic stressors, particularly excessive intake of oxidized and omega-6-enriched lipids, activate NF-κB and NLRP3-dependent inflammatory pathways in macrophages, thereby fostering a pro-tumorigenic and pro-atherogenic microenvironment. We underscore the emerging role of microRNAs as functional mediators connecting lipid metabolism, inflammation, and cellular plasticity across atherosclerotic and neoplastic tissues. These non-coding RNAs modulate key signaling pathways, including the critical PI3K/Akt, NFκB, and TGFβ axes, thereby promoting macrophage phenotype shifts, endothelial dysfunction, aberrant proliferation, and immune evasion. Importantly, interventions aimed at restoring lipid homeostasis, including Mediterranean-style diets, caloric restriction, and regular physical activity, act as important regulators of systemic and tissue-specific inflammation. Nutritional interventions increase monounsaturated and omega-3 fatty acid content and limit oxidized lipid exposure. We propose that combining metabolic modulation with RNA-based therapies, such as miRNA mimics or inhibitors delivered through nanoparticles or pH-responsive peptide systems, may offer synergistic avenues for controlling metabolic inflammation in both cancer and cardiovascular disease. Future research should focus on the targeted and context-dependent regulation of non-coding RNA networks within immuno-metabolic circuits, advancing precision medicine in cardio-oncology.

Lactylation, a recently recognized post-translational protein modification, is reshaping research in epigenetics and molecular medicine. Emerging evidence indicates that lactylation plays a critical role in the onset and progression of cancer, as well as in several pre-cancerous and metabolism-associated pathologies. This review summarizes the current understanding of the mechanisms and biological roles of lactylation in cancer and other diseases. Lactate has been shown to promote carcinogenesis both as an additional energy source and as a signaling molecule. Glycolysis and glucose transport-major sources of lactate and subsequent lactylation-are frequently targeted by anti-cancer therapies. Several small-molecule glucose transporter type 1 (GLUT1) inhibitors, including STF-31, WZB-117, and BAY-876, have demonstrated efficacy in suppressing tumor growth. During lactylation, lactate is covalently attached to histone lysine residues, leading to epigenetic modifications. This process is regulated by "writer" enzymes (p300 and HBO1) and "eraser" enzymes (HDAC1-3 and SIRT1-3), which participate in nuclear signaling networks associated with oncogenic transformation. Several inhibitors targeting "writer" enzymes, such as A485 and andrographolide, have been developed and shown to suppress angiogenesis. Inhibition of tumor immune evasion has also been explored using glycolytic enzyme inhibitors, including 2-deoxy-D-glucose and oxalate. Despite these advances, lactylation-targeted research remains in its early stages and faces notable limitations that warrant further investigation. This review provides insights into the role of lactylation in diverse diseases and highlights emerging therapeutic strategies aimed at modulating lactylation-associated molecular targets.

Obesity is associated with an increased risk of developing breast cancer, particularly in postmenopausal women, through mechanisms such as excessive estrogen production, insulin resistance, and chronic low-grade inflammation, all of which promote tumor initiation and progression. Alterations in the gut microbiota, frequently observed in obesity, further exacerbate this risk by influencing estrogen metabolism, modulating immune responses, and promoting systemic inflammation, thereby creating a microenvironment conducive to breast cancer growth. Medical nutrition therapy plays a crucial role in managing these interrelated conditions, with dietary interventions such as the Mediterranean diet, ketogenic diet, and intermittent fasting showing potential to reduce weight, improve metabolic health, modulate the gut microbiome, and positively influence inflammatory and hormonal signaling. While short-term outcomes are promising, long-term studies are required to confirm their effects on breast cancer survival and recurrence. Personalized nutrition-accounting for genetic, epigenetic, and microbiome profiles-is emerging as a highly effective approach to enhance therapeutic outcomes. Integrating targeted nutritional strategies into breast cancer treatment protocols is essential to improve prognosis, optimize therapy responses, and enhance patients' quality of life. This narrative review examines the role of nutritional therapies in the prevention and management of obesity and breast cancer, emphasizing their impact on tumor biology, treatment efficacy, and patient health.

Cellular plasticity refers to the ability of healthy cells to shift between phenotypic states and modify their characteristics to maintain tissue homeostasis and integrity. In the tumor context, cancer stem cells (CSCs) exploit this flexibility to withstand stress, facilitate tumor dissemination, and evade therapeutic interventions. Epigenetic regulation, particularly DNA methylation at CpG sites, is recognized as a well-known driver of tumor plasticity by repressing differentiation programs through modulation of chromatin accessibility. More recently, RNA modifications (epitranscriptomics) have emerged as crucial post-transcriptional regulators of gene expression that shape RNA fate and function. Among these, N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), and N7-methylguanosine (m7G) contribute to the regulation of cell identity by modulating stemness-differentiation balance, stress adaptation, and epithelial-to-mesenchymal transition (EMT). Notably, dysregulation of both DNA and RNA methylation signatures is frequently observed in tumors, suggesting potential functional interactions between these regulatory layers. Emerging evidence indicates that DNA CpG methylation and RNA methylation pathways may cooperate to influence stemness, survival, and EMT-associated signaling, thereby supporting CSCs' plasticity. Although the molecular mechanisms underlying this crosstalk remain incompletely understood, accumulating studies suggest that DNA and RNA methylation could converge within interconnected regulatory networks that contribute to the control of cancer cell identity. A deeper understanding of these interactions may uncover novel vulnerabilities for targeting tumor plasticity. In this review, we summarize the current knowledge on the interplay between DNA and RNA methylation in regulating tumor plasticity, highlighting emerging mechanistic insights, functional interactions, and potential implications for future epigenetic and epitranscriptomic therapeutic strategies.

Statins, traditionally used for managing hypercholesterolemia, have emerged as promising agents for cancer therapy. By targeting the mevalonate pathway-a cornerstone of cellular metabolism and tumorigenesis-statins disrupt critical processes for cancer cell survival and proliferation. Some of these processes include cholesterol biosynthesis, protein prenylation, and post-translational modifications. This review discusses repurposing statins for cancer treatment given their anti-tumoral effects across many cancers, including breast, prostate, colorectal and hepatocellular carcinoma. Despite statins' ability to induce apoptosis or autophagy, arrest cell cycle, or modulate favorable epigenetic reprogramming, their efficacy is highly context-dependent, influenced by cancer type, molecular subtype and genetic variations. Challenges such as statin resistance, low bioavailability and pharmacokinetic variability further complicate their application in oncology. Nonetheless, emerging strategies, including nanoparticle-based drug delivery systems and combination therapies with chemotherapy, radiotherapy or immunotherapy, appear to help overcome these limitations. Despite encouraging preclinical findings, clinical evidence remains tantalizingly inconsistent. Future research should prioritize identifying biomarkers of statin sensitivity and optimizing nanoformulations to enhance tumor targeting while minimizing toxicity. Ultimately, statins represent an attractive opportunity to expand the anti-tumor armamentarium and highlight innovative treatment paradigms integrating metabolic modulation to precision oncology.

Extracellular vesicles (EVs) are emerging as pivotal mediators of tumor progression, metastasis, and therapy resistance, reflecting the dynamic complexity of the tumor microenvironment. Their stability in biofluids makes EVs promising candidates for both tailored cancer therapies and liquid biopsy-based cancer diagnostics. However, their nanoscale size and molecular heterogeneity continue to challenge standardized isolation and analysis. Recent advances in microfluidic and organ-on-chip technologies are transforming EV research by enabling high-resolution separation, label-free detection, and real-time monitoring within physiologically relevant microenvironments. These platforms not only enhance analytical precision but also recapitulate tumor-stromal interactions that govern EV biogenesis, trafficking, and uptake. When coupled with complementary methods (such as immunoaffinity capture, size-exclusion chromatography, and viscoelastic or magnetophoretic sorting) microfluidic systems offer unprecedented control over EV isolation and characterization. Moreover, emerging wearable microfluidic devices and metabolic labeling strategies open new avenues for personalized EV delivery and nascent vesicle tracking in cancer models. Real-time monitoring of EV transfer between cancer and stromal cells within microfluidic environments further deepens our understanding of EV-mediated communication and its role in metastatic niche formation. In this review, we highlight the latest technological innovations and translational perspectives in EV isolation and analysis, emphasizing how microfluidic platforms are reshaping cancer diagnostics and therapy. Thanks to microfluidics, these integrated systems hold promise for accelerating the clinical deployment of EVs as functional biomarkers and therapeutic agents in precision oncology and nanomedicine-based cancer treatment.

Richter transformation (RT) is a relatively rare but clinically challenging event in the natural history of chronic lymphocytic leukemia (CLL), characterized by the abrupt transformation of CLL into an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL). RT is diagnosed through histopathological confirmation, often prompted by clinical signs such as rapid lymph node enlargement, B symptoms, and elevated metabolic activity on PET-CT. Its incidence ranges from 2 % to 10 % over the CLL course, with higher risk in patients harboring specific high-risk (immuno)genetic features. Clonal relationship to the original CLL clone is crucial to understand the biology of the disease and may guide treatment decisions and anticipate RT evolution. Biologically, RT is driven by genomic instability, loss of cell cycle control, MYC activation, NOTCH alterations, and immune evasion mechanisms, including PD-1/PD-L1 upregulation. Transformation timing varies, occurring either early or late in the CLL course, may be preceded by a phase of accelerated disease, and their seeds may be traced back years before their clinical manifestation. Preclinical models, including genetically engineered mice and patient-derived xenografts, have been instrumental in elucidating the molecular underpinnings of RT, assess its interactions with the tumor microenvironment -including through the B-cell receptor-, and offer platforms for testing novel therapeutic strategies. In this review, we will deepen into the biology and evolution of DLBCL-type RT, revisiting recent publications and discussing new avenues for research in this paradigmatic evolution of CLL.

The microbiota has emerged as a pivotal modulator of cancer immunotherapy, offering novel insights into the efficacy and toxicity of immune checkpoint inhibitors (ICIs). Recent evidence highlights that microbial communities and their metabolites dynamically regulate host immunity by priming dendritic cells, enhancing T-cell infiltration, and reprogramming the tumor microenvironment. Microbiome dysbiosis is implicated in immune-related adverse events (irAEs), underscoring its dual role in therapeutic outcomes. Leveraging these findings, precision microbiome interventions, including fecal microbiota transplantation, engineered probiotics, and dietary modulation, which demonstrate potential to enhance ICIs responsiveness and mitigate irAEs in preclinical and early-phase clinical studies. However, translating these strategies into clinical practice requires rigorous validation through multicenter trials to establish safety, efficacy, and standardized protocols. This review synthesizes current knowledge on the microbiome-immune-oncology axis, with a focus on mechanistic underpinnings, translational challenges, and innovative therapeutic strategies. By integrating microbiome profiling with patient-specific factors, proposing a roadmap for personalized immunotherapy, aligning with the emerging paradigm of precision oncology.

Chronic lymphocytic leukemia (CLL) is a paradigmatic malignancy driven by intraclonal diversity and dynamic evolutionary processes. High-resolution genomic profiling has demonstrated that CLL progression rarely follows a linear trajectory; rather, it is characterized by a complex and evolving (sub)clonal architecture shaped by intrinsic biological features and extrinsic factors, including therapeutic pressure. Recurrent genetic alterations affect key signaling pathways and cellular processes, including B-cell receptor and NF-κB signaling, DNA damage response, RNA processing, and apoptosis. Many of these lesions arise as subclonal events and subsequently expand, thereby influencing disease progression, therapeutic resistance, and transformation. Over the past decade, the treatment paradigm in CLL has shifted from chemoimmunotherapy to targeted agents, resulting in substantial clinical benefit. Nevertheless, the emergence of therapeutic resistance remains a major challenge. In this review, we summarize current knowledge of clonal evolution and resistance mechanisms in CLL. Resistance to chemoimmunotherapy is frequently driven by genetic lesions, such as TP53 aberrations, and by expansion of resistant microclones. In contrast, targeted therapies select for distinct resistance mechanisms, such as BTK and PLCG2 mutations in patients treated with BTK inhibitors, as well as activation of alternative survival pathways. We further discuss emerging technologies, including single-cell sequencing and integrative multi-omics approaches. Finally, we highlight the need for future studies addressing resistance in evolving clinical contexts, such as combination targeted therapies, bispecific antibodies, and CAR T-cell therapy. Taken together, a deeper understanding of clonal evolution is central to the development of personalized therapeutic strategies and to improving long-term outcomes for patients with CLL.

Obesity and type 2 diabetes mellitus are increasingly recognized as important risk factors for cancer development and progression, including cancers of the digestive system. Indeed, epidemiologic evidence demonstrated that both conditions increase the risk of digestive system cancer incidence and mortality, although with sex-specific and ethnic variations for certain associations with specific types of cancers. While these associations were quite consistent, study design and quality differences, lack of uniform adjustment for confounding factors, heterogeneity and various biases require caution when interpreting the results. The intricate processes by which these two closely related metabolic diseases contribute to carcinogenesis involve increased substrate availability and metabolic dysregulation that create a cellular microenvironment permissive to the activation of multiple signaling pathways that contribute to tumor growth and proliferation. This review thoroughly explores the complex interplay of metabolic and inflammatory mechanisms underlying these processes, including hyperglycemia, insulin resistance, altered insulin‑like growth factor-1 signaling, dysregulated adipokines, hormonal imbalance, gut dysbiosis, chronic inflammation and altered immune response, altered mitochondrial function and oxidative stress, circadian rhythm disruption, altered autophagy. Nevertheless, most mechanistic evidence derives from in vitro systems or non-human animal models which may not fully replicate human pathophysiology and disease, and thus extrapolation to human cancer risk should be made cautiously. Given this complex mechanistic interplay, it is evident that obesity and T2DM-associated metabolic alterations play an important role in carcinogenesis, highlighting the need for targeted prevention strategies in high-risk populations, such as weight management and glycemic control, to mitigate cancer burden.

Tumor heterogeneity-encompassing diverse cellular phenotypes, genomic alterations, and microenvironmental contexts-is a principal barrier to effective cancer therapy. Single-cell RNA sequencing (scRNA-seq) has transformed our ability to resolve this complexity by capturing transcriptomes at single-cell resolution. Here, we review the technical foundations required for high-quality scRNA-seq studies. We then trace the evolution of scRNA-seq platforms from manual micromanipulation to high-throughput systems, and describe the computational pipelines that enable reliable data interpretation. The application of scRNA-seq is exemplarily shown in the context of lung cancer, where single-cell profiling has revealed (i) the clonal and sub-clonal architecture of tumors, (ii) extensive remodeling of the immune microenvironment, iii) key mechanisms underlying resistance to targeted agents and immune-checkpoint blockade, and (iv) the dynamics of neo-antigen-specific T-cell responses. Integrating machine-learning techniques-such as deep-learning classifiers and graph-based models-with single-cell transcriptomic data has markedly sped up biomarker discovery, produced more accurate risk-stratification scores, and enabled the generation of patient-specific therapeutic predictions. We surveyed the major trial registry ClinicalTrials.gov and identified ∼380 ongoing or completed studies that explicitly incorporate scRNA-seq as a correlative or pharmacodynamic endpoint. Overall, the analysis shows that scRNA-seq becomes an increasingly important component of modern trials, providing high-resolution cellular and molecular readouts that complement conventional imaging and bulk-omics endpoints. While key challenges remain, ranging from costs, scalability and need for rigorous validation before routine clinical deployment, ongoing technological advances continue to expand the potential of scRNA-seq as a cornerstone of precision medicine.

Signaling lipids have been shown to play multifaceted roles ranging from cell proliferation, metabolism, invasion, migration, and apoptosis. Mechanistically, these enzymes and their downstream targets constitute complicated and intertwined lipid signaling networks with multiple nodes of interaction and cross-regulations. Dysregulated lipid metabolism is one of the hallmarks of cancer. Targeting such lipid metabolism is a potential anticancer strategy. Several natural products and miRNAs have been reported to modulate cancer cell fatty acid (FA) metabolisms; however, the integrated connections between these natural products, miRNAs, and targets have yet to be evaluated in detail. This review uses the bioinformatic STRING tool to explore target-target interactions between Google Scholar-retrieval targets of dysregulated FA metabolism in cancer cells. miRNAs and natural products that dysregulate FA metabolism were also retrieved and connected to the STRING-target network with Google Scholar and the bioinformatic databases (miRTarBase and miRDB), which retrieves targets for miRNAs. Moreover, the knowledge gaps between miRNA- and natural product-modulated FA metabolism are intricately connected. Consequently, this review highlights and shows interactions within the natural product-miRNA-target axis in counteracting the dysregulated FA metabolism in cancer cells.

Spatial multi-omics has emerged as a transformative approach in biomedical research, enabling the integration of diverse molecular modalities while preserving their native spatial contexts. This review provides an overview of spatial multi-omics technologies, focusing on data acquisition, quality management, and integration strategies across transcriptomic, genomic, epigenomic, proteomic, and metabolomic layers. Spatial transcriptomics is highlighted as a foundational framework for aligning multi-omics data with histological and cellular architecture. We emphasize its applications in elucidating tumor heterogeneity, immune-stromal interactions, and metabolic or epigenetic dynamics within the tumor microenvironment, which are crucial for understanding disease progression and therapeutic response. The review further discusses key challenges such as technical noise, batch effects, and the complexity of high-dimensional data integration, along with optimization strategies for sampling and analysis in both clinical and research settings. Ethical and regulatory considerations, including patient data privacy and responsible implementation of artificial intelligence, are also examined in the context of clinical translation. Taken together, this review offers an integrative synthesis of spatial multi-omics technologies and their applications in cancer biology, providing a balanced perspective to help researchers and clinicians navigate this rapidly evolving field and recognize its translational potential for advancing precision medicine.

Sarcomas and carcinomas represent approximately 1% and 80% of all cancer diagnoses, respectively. Despite their very different prevalence, both tumor types share a critical dependence on mitochondrial functions for metabolic adaptation, survival and progression. Mitochondria act as cellular powerhouses by generating ATP through oxidative phosphorylation; however, their roles extend far beyond energy production. These organelles are central hubs of biosynthetic and catabolic pathways, including the tricarboxylic acid cycle, glutaminolysis, lipid metabolism, branched-chain amino acid catabolism and gluconeogenesis. Moreover, they play a key role in regulating various forms of programmed cell death, such as apoptosis, necroptosis, ferroptosis and pyroptosis. In this review, we provide a comprehensive overview on the contribution of mitochondria to tumor cell metabolism specifically in sarcomas and carcinomas. We describe how mitochondrial DNA-encoded proteins influence tumorigenesis and how mitochondria support cancer stem cell maintenance. We also discuss the therapeutic potential of targeting mitochondrial pathways, highlighting clinical trials and emerging strategies. The available evidence suggests that sarcoma cells might be more responsive to mitochondrial-targeted therapies due to their higher mitochondrial content and activity compared with carcinomas. Lastly, we bring some evidence of the involvement of mitochondria in the tumor microenvironment and discuss the implication of this finding for cancer immunotherapy. Altogether, these insights emphasize the importance of mitochondria as central regulators of cancer cell fate and promising therapeutic targets.

Glioblastoma (GBM) remains the most lethal primary brain tumor in adults. These aggressive tumors evolve as dynamic, spatially organized ecosystems in which tumor cells continuously interact with the surrounding brain parenchyma and systemic environment. These reciprocal interactions actively drive invasion, therapeutic resistance, and ultimately, inevitable recurrence. Modelling this level of complexity has long required significant compromise. GBM organoids have emerged as a promising intermediate platform, bridging the gap between costly, low-throughput animal models and overly simplistic two-dimensional in vitro cultures. In this review, we summarize the diverse protocols currently used for GBM organoid derivation and long-term maintenance, focusing on the recapitulation of microenvironmental traits. We further discuss how these systems enable the investigation of tumor niche architecture and dynamic crosstalk with key components of the tumor microenvironment, including neural and immune elements, vascular-associated signals, and extracellular matrix cues. Although the inherent limitations of ex vivo systems must be carefully considered, increasingly advanced and well-designed protocols will enable robust interrogation of interactions within the GBM ecosystem and provide powerful platforms for therapeutic testing.