Search Results (502)

Patient-derived organoids (PDOs) provide ex vivo functional models that capture tumor drug-response patterns across multiple cancer types. Organoid drug sensitivity testing (ODST) has accumulated supportive evidence in single-tumor studies, yet it lacks a pan-cancer biostatistical framework that can support multi-cancer clinical decision-making. This article presents a pan-cancer ODST validation framework that integrates evidence synthesis, regulatory mapping, and adaptive trial design. The framework specifies analytical-performance standards, a three-stage validation architecture, and an explicit cross-tumor portability coefficient that quantifies the transferability of validated evidence among cancer types. Implementation barriers, including heterogeneous tissue-collection standards, variable establishment success, immunotherapy modeling limitations, and regulatory misalignment, are identified, and corresponding mitigation strategies are described. The framework supports a structured pathway from analytical validity to clinical utility for ODST across solid-tumor indications. Full article

Background: Conventional drug delivery systems often lead to fluctuating plasma concentrations (“Peak and Trough” phenomenon), causing toxicity or inefficacy. Microfluidics has emerged as a revolutionary tool to overcome, among other applications, the limitations of conventional bulk encapsulation methods, such as polydispersity and poor reproducibility. Methods: A systematic review of the literature published between 2020 and 2025 was conducted to evaluate the application of microfluidics in the synthesis of advanced nanomedicines. The review focused on Lipid Nanoparticles (LNPs), Polymeric Nanoparticles (PNPs), and Hydrogel Microspheres. Results: Microfluidics enables the production of monodisperse particles with precise control over geometry and drug loading stoichiometry. Key therapeutic applications include oncology (passive and active targeting), gene therapy (mRNA vaccines), and regenerative medicine (diabetic wound healing). Conclusions: While microfluidics offers superior quality control compared to bulk methods, industrial scalability remains the primary challenge, currently addressed through parallelization and continuous flow strategies. Full article

The introduction of minimally invasive surgery (MIS) marked a turning point in the history of medicine, driving one of the sharpest declines in surgical mortality and morbidity ever recorded—saving millions of lives and sparing an estimated one billion patients the suffering once inherent to large-incision surgery. Within a single generation, this once highly contested surgical innovation became the global standard of care, transforming surgical practice across disciplines and on a global scale. By every measure of public health, these outcomes place modern minimally invasive and robotic-assisted surgery as among the most consequential life-saving advances in modern medical history. This review examines the clinical impact and global dissemination of MIS, tracing its evolution from Camran Nezhat’s pioneering expansion of laparoscopy beyond diagnostics to complex therapeutic procedures across surgical disciplines. Drawing on decades of evidence across gynecology, general surgery, and urology, we show that MIS is associated with substantial reductions in perioperative mortality, major complications, blood loss, infections, thromboembolic events, postoperative pain, and length of hospital stay, while maintaining oncologic equivalence and improving functional and quality-of-life outcomes. Beyond these technical advances, MIS catalyzed a broader reimagining of surgery itself, challenging long-standing norms rooted in large-incision approaches and shifting the field toward precision, organ preservation, and pathology-directed intervention. These changes were accompanied by parallel advances in multiple domains, including in imaging, intraoperative visualization technologies, surgical anatomy, instrumentation, and nerve- and organ-sparing techniques—developments that collectively established the foundation for contemporary minimally invasive and robotic-assisted surgery. Collectively, these advances have contributed to the prevention of an estimated 10–20 million surgery-related deaths that would likely have occurred under the large-incision approaches of the past. Full article

Non-Hodgkin lymphoma (NHL) encompasses a biologically diverse group of malignancies for which the integration of precision medicine has markedly reshaped therapeutic strategies. Recent advances in molecular profiling, target identification, and drug development have led to the introduction of highly selective agents capable of overcoming resistance mechanisms and improving outcomes in relapsed or refractory disease. This review highlights three targeted therapies—pirtobrutinib, brentuximab vedotin, and belinostat—and their evolving roles in modern NHL management. Pirtobrutinib, a next-generation, non-covalent Bruton tyrosine kinase (BTK) inhibitor, demonstrates preserved activity in patients previously treated with covalent BTK inhibitors (BTKi), addressing a critical unmet need in B-cell lymphomas. Brentuximab vedotin, an antibody–drug conjugate targeting CD30, has significantly improved therapeutic precision by delivering cytotoxic agents directly to lymphoma cells and has become a central component of treatment for CD30-expressing NHL subtypes. Belinostat, a broad-spectrum histone deacetylase (HDAC) inhibitor, offers a mechanistically distinct epigenetic approach, particularly in peripheral T-cell lymphomas (PTCL), where conventional chemotherapy has limited efficacy. Together, these agents exemplify three complementary paradigms of precision oncology in NHL: kinase signaling inhibition, antigen-directed cytotoxic delivery, and epigenetic modulation. This review synthesizes current evidence, clinical trial data, and future perspectives regarding the integration of pirtobrutinib, brentuximab vedotin, and belinostat into evolving treatment paradigms. Cumulatively, these therapies illustrate both the progress and the ongoing challenges of biomarker-driven treatment in NHL, including resistance mechanisms, toxicity management, optimal therapeutic sequencing, and variability in evidence maturity across targeted strategies. While pirtobrutinib and brentuximab vedotin are supported by increasingly robust clinical evidence in selected lymphoma subtypes, the role of belinostat remains constrained by modest response rates and limited randomized data, underscoring the continued need for biomarker refinement and more precisely individualized therapeutic approaches in NHL precision medicine. Full article

Allostatic load (AL) is a multisystemic indicator of the cumulative “wear and tear” on the body caused by chronic stress. In oncology, high AL is associated with a poorer prognosis, a higher number of postoperative complications, and lower treatment tolerance. Patients with head and neck cancer (HNC)—due to frequent smoking, alcohol abuse, low socioeconomic status, and high psychological and functional burden—belong to a group particularly vulnerable to high AL; however, its role in this population remains poorly understood. This narrative review includes publications from 2015 to 2026 from the PubMed/MEDLINE, Embase, and Scopus databases. We analyzed original studies, systematic reviews, and narrative reviews concerning AL in oncology, prehabilitation, and HNC. Additionally, we employed the snowballing method and included studies from key research groups. The results reveal a clear research gap—the lack of direct studies evaluating AL in HNC patients. In other cancers (breast, colorectal, lung), high AL is an independent risk factor for complications, longer hospital stays, and poorer survival. Multimodal prehabilitation (exercise, nutritional, and psychological support) shows potential for reducing AL, but no prospective studies evaluating this effect have been conducted in the HNC population. Assessment of AL may serve as a valuable tool for preoperative risk stratification and monitoring the effects of prehabilitation in patients with head and neck cancer. Prospective cohort and randomized trials are needed to integrate AL into precision medicine for this patient group. Full article

Background: The growing complexity and cost of oncohematological treatments has created an urgent need for standardized methodologies capable of enabling inter-institutional comparisons of healthcare expenditure within homogeneous patient groups. Cancer-related pharmaceutical costs vary substantially depending on tumour type, disease stage, and therapeutic approach, making cross-institutional benchmarking challenging due to heterogeneity in patient populations and clinical practice patterns. Therefore, integrating cost analysis with clinically meaningful patient stratification is essential to improve resource allocation and outcome evaluation. Methods: A multicentre working group comprising four tertiary hospitals in Madrid (Spain) was established to develop and preliminarily evaluate a novel classification system for adult oncohematological patients. A standardized methodology was designed to stratify patients into homogeneous groups (PATONCO categories) based on tumor location, therapeutic objective, and clinically relevant biomarkers. A cost indicator was defined as the average cost per patient per month for each PATONCO category. Data were extracted from pharmacy dispensing systems and analyzed using descriptive and inferential statistics, including Kruskal–Wallis and post hoc Dunn tests. Results: A total of 3659 patients were included (3168 oncology; 491 hematology), distributed across 62 programmes (54 oncology; 8 hematology). The PATONCOS tool enabled the identification and validation of a cost indicator (average cost/patient/month per category), allowing inter-hospital comparison. Significant differences in costs were observed across most high-prevalence categories, reflecting variability in drug selection within homogeneous patient groups, as documented by the differential use of specific therapeutic agents across centers. The model demonstrated its capacity to detect intra-group homogeneity and inter-group variability, improving the identification of high-cost patient subgroups and supporting benchmarking across centers. Conclusions: The PATONCOS tool provides a novel, clinically oriented stratification methodology that integrates pharmacotherapy, biomarkers, and disease stage with economic evaluation. This approach enables more accurate comparisons of oncology treatment costs between institutions and may support data-driven decision-making in resource allocation. Its implementation may contribute to more sustainable healthcare systems by aligning clinical practice with economic outcomes. Full article

Chimeric antigen receptor T (CAR-T) cell therapy has transformed the treatment of hematologic malignancies, yet its broader application, particularly in solid tumors, remains constrained by high cost, labor-intensive manufacturing, limited production capacity, and variable clinical performance, as well as barriers such as poor trafficking, antigen heterogeneity, and an immunosuppressive tumor microenvironment. In vivo CAR-T cell engineering, in which CAR-T cells are generated directly within the patient, offers a paradigm shift by eliminating the need for ex vivo cell processing and complex logistical infrastructure. Among emerging approaches, messenger RNA (mRNA)-loaded lipid nanoparticles (LNPs) have emerged as a promising and clinically tractable platform for in vivo CAR-T cell generation, enabling direct reprogramming of T lymphocytes within the patient and thereby circumventing the need for leukapheresis, viral vector production, and prolonged ex vivo culture, effectively transforming the patient into their own cell therapy factory. This review synthesizes advances in mRNA-LNP-mediated in vivo CAR-T cell generation, encompassing ionizable lipid chemistry and emerging T cell-targeted delivery strategies, including surface functionalization approaches. We discuss the implications of transient CAR expression for immune activation, safety, and therapeutic durability, alongside CAR design optimization through co-stimulatory domains and safety switches. Preclinical evidence from murine tumor models and non-human primates is integrated with current regulatory considerations, and key barriers to clinical translation are highlighted. Collectively, progress in nucleic acid delivery, synthetic immunology, and precision medicine positions in vivo mRNA-CAR-T therapy as a promising modality for oncology and beyond. Full article

Folate (vitamin B9) is central to one-carbon metabolism, supporting nucleotide biosynthesis, methylation homeostasis, and epigenetic regulation. The gut microbiome both produces and consumes folate, creating a bidirectional axis influencing host health and disease. We systematically reviewed 159 original studies from MEDLINE, Google Scholar, Embase, and Scopus (inception through January 2026) examining enteric microbiota–folate interactions, with intervention evidence graded using the Oxford Centre for Evidence-Based Medicine 2011 framework. Only a minority of gut bacteria possess complete folate biosynthetic pathways; most depend on cross-feeding from prototrophic taxa including Bifidobacterium, Lactobacillus, and Streptococcus. Altered microbial folate metabolism was associated with metabolic, gastrointestinal, oncologic, neuropsychiatric, cardiovascular, immunologic, and reproductive disorders through convergent mechanisms of disrupted methylation, genomic instability, and immune dysregulation. Probiotic interventions achieved the strongest evidence, supported by multiple human controlled and observational trials and animal models. The evidence for prebiotic, dietary, and folate supplementation interventions was moderate due to the predominant animal models and in vitro data. Overall, the predominant associational and observational evidence base is insufficient to establish causal relationships, underscoring the need for adequately powered human randomized controlled trials with folate-specific endpoints, multi-omics integration, and precision approaches matching folate form and dose to individual microbiome and host genetic profiles. Full article

Background/Objectives: Providing optimized and accurate treatment to cancer patients remains a major challenge in oncology care. The emergence of precision medicine tools to match the correct therapy to the patient has significantly advanced treatment modalities in the last few years. While genomics has been shown to be critical in selecting targeted therapies for a specific somatic mutation, the overall clinical benefit of broad genomic sequencing has been found lacking. Here, we evaluate the utility of our previously clinically validated ex vivo functional assay across different treatment scenarios, demonstrating its ability to transform predicted non-responders into predicted responders, rule out ineffective treatments, provide multiple treatment options, and validate physician choices. Methods: The evaluation was performed on a post-market surveillance study analyzing 312 patients, from which 278 patients had successful test reports (an 89.1% test success rate), with clinical outcomes available from 45 of those patients. Results: We show that in the group of patients with clinical response data, the tests yield a PPV of 91.18% and NPV of 90.91% with clinical utility impacting physician decision in 51.1% of cases. Further analysis of the entire cohort showed the potential of clinical utility to reach up to 59.3% on a large group of patients. Conclusions: The accurate prediction of patient response using the test suggests the potential for the platform to improve patient treatment in clinical practice by reducing ineffective drug use and optimizing personalized patient drug regiments. Full article

Tumor heterogeneity and microenvironmental complexity remain fundamental barriers to genomics-centered precision oncology, frequently causing discordance between molecular alterations and real-world therapeutic responses. Here, we reviewed patient-derived organoid (PDO) technologies as functional platforms that complement molecular profiling by directly investigating patient-specific sensitivity, resistance, and microenvironment dependent vulnerability. We first summarize why conventional preclinical systems, two-dimensional cell lines and patient-derived xenografts, are limited by reduced biological fidelity, impractical turnaround time, and scalability for clinical decision support. We then synthesized organoid-based evidence across three representative disease malignancies with distinct precision-medicine bottlenecks. Across these settings, we highlight advances that extend the PDO capability beyond the tumor epithelium alone, including air–liquid interface cultures, immune and stromal co-cultures, and microfluidic organoid-on-chip systems, as well as integration with multi-omics and artificial intelligence for scalable analytics. Finally, we discuss the key translational requirements, standardization of culture matrices and assay readouts, quality control, automation to reduce turnaround time, and regulatory/ethical frameworks, required to transition organoid-guided testing from proof-of-concept to routine implementation. Collectively, this review reframes organoids as functional stratification platforms supporting the integration of functional response profiling alongside genomics-guided precision oncology approaches. Full article

Breast cancer is one of the most commonly diagnosed malignant tumors worldwide and represents a significant public health problem. This paper presents the characteristics of the disease, with particular emphasis on risk factors, mechanisms of development, and molecular classification. Current diagnostic methods and available therapeutic strategies, such as surgery, chemotherapy (CT), radiotherapy (RT), and targeted therapies, are discussed. Particular attention is given to nanotechnology as a promising direction for the development of modern medicine. The potential applications of nanoparticles (NPs) in the diagnosis and treatment of breast cancer are presented, taking into account their mechanisms of action, potential clinical benefits, and limitations related to safety and efficacy. NPs may contribute to increased diagnostic precision and therapeutic efficacy, indicating their significant potential in the future of oncology. Full article

Central nervous system (CNS) tumors represent a heterogeneous group of neoplasms associated with significant morbidity and mortality despite their relatively low incidence. Advances in the fifth edition of the World Health Organization (WHO) classification have emphasized the integration of histopathological, immunohistochemical, and molecular features, fundamentally transforming diagnostic and prognostic frameworks in neuro-oncology. This manuscript aims to provide an overview of CNS tumor biology, focusing on key diagnostic markers, genetic and epigenetic alterations, and emerging therapeutic strategies. It further describes recent advances in multi-omics approaches and artificial intelligence, which enable deeper characterization of tumor heterogeneity and support the development of precision medicine strategies. Finally, current and emerging therapeutic modalities, including combination therapies, targeted treatments, and novel molecular targets, are examined with emphasis on overcoming resistance mechanisms and improving clinical outcomes. Overall, the integration of molecular biology, advanced diagnostics, and innovative therapeutic approaches represents a critical step toward personalized management of CNS tumors and improved patient survival. Full article

Macrophage-derived extracellular vesicles (EVs) have emerged as promising biomimetic platforms for targeted cancer drug delivery due to their biocompatibility, immune-modulatory properties, and tumor-homing capabilities. Among macrophage subtypes, M1-polarized macrophages exhibit potent anti-tumor functions characterized by pro-inflammatory cytokine secretion, improved antigen presentation, and the ability to remodel the tumor microenvironment (TME). Utilizing these properties, M1-polarized macrophage-derived EVs serve as cell-free therapeutic systems capable of delivering bioactive cargo while simultaneously promoting anti-tumor immune responses. However, the clinical application of natural EVs is limited by low yield, heterogeneity, and challenges in large-scale production. Artificial nanovesicles (ANVs) have been developed to address these limitations, offering improved scalability, compositional control, and reproducibility. This review provides an overview of macrophage differentiation and polarization, with a focus on the immunological profile and anti-tumor mechanisms of M1-polarized macrophages. It further discusses current methodologies for EV isolation and ANV generation, along with cargo loading strategies that balance encapsulation efficiency and vesicle stability. In addition, this review also emphasizes their targeting approaches, cellular uptake pathways, and the intracellular trafficking mechanisms that influence delivery efficiency and therapeutic outcomes. Key challenges, including standardization, biological barriers, and functional consistency, are critically evaluated. Emerging strategies that integrate vesicle engineering with personalized medicine underscore the potential of these systems to advance precision oncology. Full article

Neuroblastomas remain a disproportionately morbid and mortal pediatric cancer. Representing 8% of all childhood cancer diagnoses, it still is the cause of 14% of cancer-related deaths in children despite the use of aggressive multimodal treatments with significant long-term sequelae. The development of targeted therapies for neuroblastoma has been and will continue to be the optimal approach to improve durable long-term survival in these patients while reducing the consequences of treatment. Here, I review the history of the development of targeted therapies for the treatment of neuroblastoma. I discuss the history of therapies that have been integrated into current treatment regimens, including isotretinoin, anti-GD2 antibodies and eflornithine. I review the history of candidate biologic targets in this malignancy as well as ongoing and future efforts to improve outcomes. Full article

Background: RET fusion is an actionable tumor-agnostic biomarker, but its observed frequency in routine comprehensive genomic profiling (CGP) may vary across testing platforms and clinical contexts. We conducted a nationwide descriptive analysis to benchmark observed RET fusion frequency in Japanese routine practice. Methods: This retrospective descriptive study used anonymized aggregated data from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT), including CGP-tested cases through 31 March 2025. Observed RET fusion frequency was summarized overall, across five standardized CGP platforms, across 12 prespecified organ groups, and in pooled tissue-based versus liquid-based comparisons. Exact binomial 95% confidence intervals were calculated to provide descriptive precision for low-frequency estimates. Results: Among 97,343 cases, 257 were RET-positive, corresponding to an overall observed RET fusion frequency of 0.26%. Platform-specific frequencies were 0.29% (192/66,992) for FoundationOne CDx, 0.28% (42/14,878) for FoundationOne Liquid CDx, 0.14% (6/4235) for GenMineTOP, 0.16% (15/9196) for NCC oncopanel, and 0.10% (2/2042) for Guardant360. Thoracic tumors showed the highest observed frequency (1.39%, 94/6740), followed by head and neck/thyroid tumors (1.04%, 42/4030). In a crude pooled comparison not adjusted for organ mix or clinical context, tissue-based and liquid-based CGP yielded numerically similar crude pooled frequencies of 0.265% (213/80,423) and 0.260% (44/16,920), respectively. Conclusions: This nationwide analysis benchmarks how RET-positive findings are surfaced to clinicians across heterogeneous routine CGP implementations in Japan. The data support platform-aware interpretation of RET results in practice, but should not be construed as biologic prevalence estimates or comparative assay performance. Full article