Despite undergoing transurethral resection and appropriate Bacillus Calmette-Guérin (BCG) administration for high-risk non-muscle invasive bladder cancer (NMIBC), the non-responder rate is approximately 25%. Although radical cystectomy is the gold standard of treatment recommended by various international guidelines, many patients are either unwilling or ineligible for this therapeutic option. In Argentina, keyhole limpet hemocyanin (immunocyanin KLH) is approved for those patients. The primary objectives of this study were to evaluate the overall treatment response, defined as disease-free survival (recurrence and/or local or distant progression), and adverse events.

Bladder cancer accounts for nearly 600,000 new cases and over 200,000 deaths annually worldwide. Approximately 25% of diagnoses correspond to muscle-invasive disease, and up to 50% of patients undergoing radical cystectomy experience recurrence within the first two years, with a 5-year overall survival reaching 50%-60%. Despite the use of neoadjuvant chemotherapy, clinical trials have failed to attain a considerable reduction in the risk of locoregional recurrence, which remains a major clinical challenge due to the limited and largely ineffective salvage treatment options. In this context, adjuvant radiotherapy (ART) has re-emerged as a potential strategy for reducing locoregional recurrence and improving metastasis-free survival, supported by advances in delivery techniques and a reassessment of safety concerns following the BART trial. Simultaneously, perioperative immunotherapy is reshaping the therapeutic landscape of muscle-invasive bladder cancer, with recent studies, such as CheckMate 274 and NIAGARA, establishing a new standard of care. The novelty of this review lies in the integration of the evolving role of ART within the immunotherapy era, with critical examination of its complementary value, toxicity profile and patient selection in light of modern systemic strategies. This narrative review provides an updated synthesis of current evidence and ongoing trials and offers a perspective on how ART can be optimally incorporated into multimodal management of high-risk bladder cancer.

Management of metastatic prostate cancer (mPCa) poses significant challenges due to inherent tumor heterogeneity and therapeutic resistance. Advances in molecular imaging, liquid biopsies, and biomarkers are enabling precision oncology, while artificial intelligence (AI), including machine learning (ML) and deep learning (DL), integrates complex datasets to improve diagnostic accuracy, risk stratification, and treatment guidance. This review highlights AI's applications in mPCa, focusing on imaging, cell-free nucleic acids, circulating tumor cells, and genomic classifiers. We emphasize AI's role in enhancing diagnostics and personalizing treatments, with implications for improving clinical outcomes through better decision-making. Finally, we discuss opportunities and challenges in deploying AI systems, stressing multimodal integration and validation for real-world clinical impact.

Cancer stem cells (CSCs) contribute to an immunosuppressive microenvironment through complex mechanisms and tumor-immune interactions. However, the key determinants of CSC characteristics in driving tumor progression, immune suppression, and response to ICIs remain unclear and require systematic investigation. This study developed a quantitative systems pharmacology (QSP) model covering various CSC properties, thereby capturing the temporal dynamics and CSC-immune interactions in triple-negative breast cancer (TNBC). Using the unified longitudinal dataset of tumor growth, CSC frequency, and immune cell dynamics that we obtained from BALB/c mice bearing wild-type or Cd274-knockout 4T1 cells under various inoculation conditions, which provides multi-dimensional insights into CSC-related biology, the QSP model was calibrated and validated. Simulations and sensitivity analysis indicated that TNBC tumors with strong stemness exhibited significantly accelerated tumor growth and reduced infiltration of cytotoxic immune cells such as cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. These were associated with CSCs' enhanced self-renewal capacity, stemness maintenance, secretion of transforming growth factor beta (TGF-β) and vascular endothelial growth factor (VEGF), and PD-1/PD-L1-mediated immunosuppression. ICIs showed minimal efficacy in tumors with enhanced stemness, which was also linked to the aforementioned characteristics. Both the administration sequence and initiation timing of ICIs differentially influenced the therapeutic outcomes. These findings elucidate the roles of CSCs in TNBC progression, tumor immunity, and ICI efficacy while identifying the key underlying CSC characteristics, suggesting the potential value of assessing CSC biomarkers or abundance before ICI treatment and support the development of ICIs and anti-CSC combination therapies.

BACKGROUND Mycosis fungoides, the most common cutaneous T-cell lymphoma, can transform into large cell lymphoma in some cases, leading to worse outcomes and reduced life expectancy. CASE REPORT We report the case of a 38-year-old Brazilian man with a history of multiple skin lesions refractory to medical treatment, requiring repeated hospitalizations, procedures, chemotherapy, phototherapy, and immunotherapy. The patient was followed by the same hospital's pathology and dermatology services for 17 years, from the diagnosis of mycosis fungoides to subsequent transformation to large cell lymphoma and eventual death. CONCLUSIONS We report a rare condition with a poor prognosis, highlighting the challenges associated with disease transformation, which markedly reduces patients' life expectancy and quality of life. The histological findings and association with the clinical manifestations were vital to the diagnosis and treatment of the disease; thus, early biopsy - even in young patients - is recommended, as it may reveal a new differential diagnosis and influence prognosis. Since the evolution of mycosis fungoides to large cell lymphoma after the transformation process is extremely aggressive, we emphatically recommend initial and follow-up biopsies even in younger patients without prior comorbidities, as in the present case. Increased awareness among clinicians regarding atypical presentations, particularly in populations not typically considered at risk, such as our patient, may also contribute significantly to timely intervention and more favorable outcomes.

Multiple myeloma (MM) is an incurable hematological malignancy with excessive bone marrow infiltration and pro-inflammatory microenvironment. In clinical practice, melphalan, an alkylating agent, and dexamethasone, a glucocorticoid widely used in MM regimens, provide clinical benefits. However, their efficacy is still limited by systemic toxicity, poor tumor selectivity, and the difficulty maintaining a predefined drug ratio at the tumor site. To address these challenges, we designed a supramolecular peptide-drug conjugate prodrug nanosystem (HMD NPs) composed of β-cyclodextrin-modified hyaluronic acid (HA-β-CD) scaffold and dual-drug conjugates, Ada-M-GFLG-D. In this design, MA and DEX are conjugated via a cathepsin B-cleavable GFLG linker and functionalized with adamantane for host-guest assembly, which allows co-delivery of the two drugs at a fixed 1:1 stoichiometric ratio. The resulting HMD NPs exhibited excellent stability, efficient cellular uptake. Ada-M-GFLG-D remains encapsulated within nanoparticles under physiological conditions. However, upon exposure to MM-mimicking intracellular conditions, HMD NPs undergo an enzyme-activation process, rapidly releasing both drugs. Cellular experiments demonstrate potent anti-tumor effects and significant downregulation of inflammatory pathways. In animal models, HMD NPs markedly suppress tumor progression, reducing bone marrow infiltration, relieving osteolytic damage, and showing favorable biocompatibility. These findings provide a promising strategy for improving therapeutic efficacy against MM.

Pancreatic ductal adenocarcinoma (PDAC) is the most malignant tumor with dismal prognosis. The chemotherapy effect of PDAC is limited and has severe side effects. Hence, identifying a natural leading compound with high efficacy against PDAC is urgently needed. Chrysanthemum morifolium (C. morifolium), a traditional Chinese medicinal herb with reported antitumor properties, was hypothesized to contain polysaccharides with therapeutic efficacy against PDAC. A novel homogeneous RG-I pectin, HJ222, was successfully isolated and purified. Structural analysis shows that HJ222 possesses a backbone composed of repeating →2-α-Rhap-(1 → 4)-α-GalpA-(1 → units, with side chains extending from the O-4 position of 2,4-α-Rhap and certain 3,4-α-GalpA residues, forming galactose- and arabinose-rich branches. In vitro and in vivo assays demonstrate that the sulfated derivative S3HJ222 of HJ222 can significantly suppress pancreatic cancer cell proliferation and completely retard tumor growth in patient-derived xenograft mouse models. Mechanistic studies reveal that S3HJ222 can induce ferroptosis-a non-apoptotic form of cell death-by elevating intracellular Fe2+ and reactive oxygen species (ROS). Furthermore, S3HJ222 directly binds and stabilizes transferrin receptor (TFRC), and activates the acyl-CoA synthetase long-chain family member 4 (ACSL4) signaling axis. Collectively, S3HJ222 may be a promising active compound for the development of new anti-PDAC drugs.

Tumor heterogeneity, immunosuppression, and frequent adverse effects present major challenges in colorectal cancer therapy. Although the combination of oxaliplatin (OXA, chemotherapy) and fruquintinib (FRU, antiangiogenic) shows clinical promise, their divergent physicochemical properties and inadequate tumor selectivity lead to suboptimal efficacy and systemic toxicity. To overcome the challenge, we developed a tumor-targeted nanosystem based on chitosan and fucoidan for co-delivery of hydrophilic oxaliplatin and hydrophobic fruquintinib (CS-Arg/Fuc-Bio@OF). The nanoparticle leverages the inherent P-selectin affinity of fucoidan and active targeting given by biotin modification to achieve precise tumor accumulation and microenvironment-responsive drug release. In vitro studies demonstrated that CS-Arg/Fuc-Bio@OF effectively eliminated HCT116 and HT29 cancer cells by inducing robust immunogenic cell death (ICD) and exerted potent anti-angiogenic effects. The combination of OXA-induced ICD with FRU-mediated angiogenesis suppression and polysaccharide-promoted immunomodulation synergistically reprogrammed the immunosuppressive tumor microenvironment, facilitating an effective anti-tumor immune response. In vivo, the nanoparticles significantly inhibited tumor growth and demonstrated good biosafety, with a hemolysis rate < 5% and no appreciable organ toxicity observed. This work not only validates CS-Arg/Fuc-Bio@OF as an efficient and safe combination therapy carrier but also provides a novel strategy for developing drug delivery systems based on natural polysaccharides.

The local immune effects of cancer radiotherapy remain poorly characterized in humans due to limited access to irradiated tissue. Mechanistic insights largely derive from preclinical models employing tumor-intact, neoadjuvant-like settings. Here, we present real-world immunoprofiling data from breast cancer patients undergoing breast-conserving surgery with (n = 20) or without (n = 29) intraoperative radiotherapy (IORT). Postoperative wound fluid samples were analyzed by flow cytometry, multiplex cytokine profiling, and bulk RNA-sequencing, alongside systemic immune monitoring in peripheral blood. IORT triggered rapid local accumulation of distinct innate immune cell subsets and cytokines mediating recruitment, activation, and innate-adaptive crosstalk, accompanied by systemic features consistent with emergency hematopoiesis. Transcriptomic profiling of wound fluid mononuclear cells revealed enrichment of proinflammatory IL-6-JAK/STAT3 signaling. In vitro, irradiation of primary breast tissue cells recapitulated key cytokine patterns and led to robust senescence induction, suggesting irradiated, senescent normal tissue cells as drivers of early immune activation in postsurgical radiotherapy. These data provide direct clinical evidence that radiotherapy shapes local and systemic immune responses, offering mechanistic insights with clear relevance for tumor immunology and the development of rational radiotherapy‒immunotherapy combination strategies.

Glioma is a highly invasive and drug-resistant malignant primary tumor. Increasing research is focusing on the function of neutrophil extracellular traps (NETs) in glioma progress. We aimed to explore the mechanism of NETs-related genes (NETs-RGs) in glioma to find potential biomarkers for glioma.

Tumor necrosis factor receptor-associated factor interacting protein (TRAIP) has emerged as a critical regulator of multiple oncogenic processes across various malignancies. However, its specific functional role and underlying mechanisms in breast cancer pathogenesis remain to be fully elucidated. Integrated bioinformatics analysis of TCGA and GTEx datasets was performed to assess TRAIP expression patterns. Complementary experimental validation was conducted using immunohistochemistry, qRT-PCR, and western blot in clinical specimens. Functional characterization of TRAIP in breast cancer cells was achieved through CCK-8 proliferation assays, colony formation analysis, transwell migration/invasion tests, wound healing experiments, and flow cytometric apoptosis detection. Mechanistic investigations employed co-immunoprecipitation and ubiquitination assays to delineate the TRAIP-PLSCR4 interaction, supplemented by rescue experiments to confirm functional interdependence. Consistent overexpression of TRAIP was observed in breast cancer tissues compared to normal controls. Genetic knockdown of TRAIP significantly attenuated malignant phenotypes, including: (1) reduction in cellular proliferation, (2) decrease in colony-forming capacity, (3) reduction in migratory/invasive potential, and (4) increase in apoptosis rates (Annexin V staining). Mechanistically, TRAIP functioned as an E3 ubiquitin ligase mediating proteasomal degradation of PLSCR4 through K48-linked polyubiquitination (co-IP validation). Notably, PLSCR4 silencing effectively rescued the tumor-suppressive effects of TRAIP knockdown. This study identifies a novel TRAIP/PLSCR4 regulatory axis in breast cancer pathogenesis, wherein TRAIP exerts its oncogenic function via ubiquitination-dependent degradation of tumor-suppressive PLSCR4. These findings position TRAIP as a promising therapeutic target for precision breast cancer interventions.

Helicobacter pylori (H. pylori) has been identified as a pathogenic factor in gastric cancer (GC). Building on our previous findings that VacA upregulates TRAF1, which in turn transcriptionally activates OASL, we explored the role of this TRAF1-OASL-PANoptosis axis in GC using clinical samples, cell lines, and mouse models. Functional assays (CCK-8, colony formation, migration, invasion, TUNEL) demonstrated that TRAF1 promotes GC cell proliferation, migration, and invasion via OASL, while suppressing apoptosis. RNA-seq revealed that upregulation of TRAF1 and OASL, combined with H. pylori infection in gastric epithelial cells, enriched pathways associated with PANoptosis. Rescue experiments showed that TRAF1 knockdown increased PANoptosis, and this increase was attenuated by the pan-caspase inhibitor Z-VAD-FMK, whereas subsequent OASL overexpression reversed the suppression of PANoptosis caused by TRAF1 knockdown, whereas LPS further induced PANoptosis. Both in vitro and in vivo models confirmed that H. pylori infection triggers PANoptosis. Co-Immunoprecipitation assays uncovered a protein interaction between OASL and the ZBP1-PANoptosome. Critically, under H. pylori infection conditions, OASL overexpression rescued the PANoptosis suppressed by TRAF1 knockdown in gastric epithelial cells. This study demonstrates that H. pylori infection induces PANoptosis, and defines a pathway wherein TRAF1 promotes PANoptosis by regulating OASL-mediated activation of the ZBP1-PANoptosome. Our findings reveal a novel, context-dependent duality of the TRAF1/OASL axis: it promotes PANoptosis, contributing to mucosal damage during the precancerous inflammatory stage, yet in established GC, this axis appears to suppress PANoptosis, facilitating tumor progression. These insights provide a theoretical foundation for targeting this pathway in treating H. pylori-associated gastritis-cancer progression.

Cancer-associated fibroblasts (CAFs) are central to the pancreatic ductal adenocarcinoma (PDAC) microenvironment, promoting tumor progression and therapeutic resistance. However, the expression landscape of CAF membrane proteins in PDAC remains poorly defined. We integrated scRNA-seq (n = 33; 87,949 cells), spatial transcriptomics (n = 2; 7,011 spots), and bulk RNA-seq (n = 7; 642 samples) to systematically identify PDAC-specific CAF membrane genes. A LASSO-based Cox model was developed to construct a prognostic signature, PaFMS, and evaluated through multi-cohort validation. Functional enrichment, immune infiltration, drug sensitivity, and immunotherapy response analyses were further conducted. Validation was performed using multiple database-driven analyses. We identified a PDAC-enriched myoCAF-c1 cluster closely associated with epithelial-mesenchymal transition (EMT) and angiogenesis. From this cluster, 33 candidate CAF membrane genes were defined, whose protein-protein interactions were predominantly linked to extracellular matrix organization and collagen remodeling, and spatially colocalized with myoCAF-c1 and EMT regions. An 11-gene prognostic signature, PaFMS that robustly stratified patients across six independent cohorts, achieving high predictive accuracy for overall survival. High-risk patients exhibited proliferative signaling activation, immune suppression, and reduced T/B-cell infiltration. PaFMS was associated with responses to 33 anticancer agents and predicted enhanced benefit from anti-PD-L1 immunotherapy in the low-risk group. Multi-cohort validation confirmed the expression specificity of PaFMS genes, including PLAU, TMEM158, and TRIM59. Together, these findings reveal that myoCAF-c1 promotes angiogenesis and tumor progression, and establish PaFMS as a robust CAF membrane-based prognostic model in PDAC with potential utility for precision prognosis and therapeutic decision-making. KEY MESSAGES: Integrated single-cell, spatial, and bulk RNA-seq analyses identified PDAC-specific CAF membrane genes. Discovered a PDAC-enriched myoCAF-c1 subtype linked to EMT and angiogenesis. Developed an 11-gene CAF membrane-based prognostic model (PaFMS) validated across six cohorts. PaFMS predicts patient survival, drug sensitivity, and immunotherapy response in PDAC.

Radioiodine therapy (RAIT) remains an essential tool in both treatment and restaging of pediatrics papillary thyroid carcinoma (PTC). Our aim was to describe the nuclear medicine management and outcomes of pediatric PTC patients over a 14-year period, within the context of their clinical and surgical characteristics, with particular emphasis on the role of radioiodine therapy in post-surgical treatment and disease restaging. A retrospective observational study was conducted at a reference Oncological Institute, including 35 pediatrics patients (< 18 years) diagnosed with PTC between 2010 and 2023. Demographic data, staging features, risk factors, surgical treatment, RAIT therapy, post-therapy scintigraphy, adverse effects, and follow-up outcomes were reviewed. Among the 35 patients (median age 15; 77% female), 54% had one or more risk factors, most frequently family history. Sixteen individuals presented low-risk disease, 12 had intermediate-risk characteristics, and 7 were classified as high-risk patients (according to ATA guidelines). Twenty-eight underwent total thyroidectomy (7 with lymphadenectomy), and the remaining received a hemithyroidectomy. Following thyroidectomy, twelve patients (all low-risk) were managed exclusively with clinical follow-up, without further directed treatment, while twenty-three patients received RAIT, with a mean activity of 3.5 GBq. Post-therapy imaging revealed previously undetected pulmonary metastases in 4 patients (17%), leading to disease upstaging. RAIT treatment resulted in complete remission in three of these cases. Adverse effects were mild and easily managed with symptomatic medication. After a mean follow-up of 9 years, no recurrences were reported, all patients were alive, and no long-term side effects were reported.

In this paper, we introduce and analyze a mechanical model for tumor growth that takes into account the life cycle of a tumor cell. The underlying process for tumor growth is the same as in classical mechanical models: the spatial expansion of the tumor is driven by the proliferation of the cells (mitosis) which is only limited by the pressure inside the tissue. The natural incompressibility of the cells, which leads to a movement of the cells away from regions of high pressure, is taken into account via a nonlinear Darcy's law. Compared to similar models studied recently, we include an additional variable, which represents the age of the cells. The various phases of the life of a cell (growth, mitosis and death) are then dependent on this age variable. We prove the existence of weak solutions and investigate their behavior numerically, focusing on the age distribution of the cells inside the tumor, the convergence to traveling wave solutions and the existence of a threshold for the death rate for expansion/regression of the tumor.

The global clinical trial landscape for multiple primary lung cancer (MPLC) exhibits a striking geographic anomaly. Through a systematic analysis of 8212 lung cancer registrations (2015-2024), we identified a cohort of 17 trials explicitly targeting MPLC. Analysis revealed an absolute geographic monopole: 100% of these trials were investigator-initiated in China, with a complete absence of active protocols in Western registries. We argue that this segregation is not accidental but driven by the "Asian phenotype",which is characterized by indolent, multifocal ground-glass nodules (GGNs), demands lung-sparing local strategies distinct from the systemic paradigms favored in the West. We urge the international community to transition from universal guidelines to phenotype-stratified management frameworks.

The tumor suppressor gene TP53 is the most frequently mutated gene in human cancers and has been a popular area of research in the field of oncology. The p53 protein, encoded by the TP53 gene, not only binds to many targeted genes but also regulates apoptosis, autophagy, cell cycle arrest, metabolism, senescence and the tumor immune microenvironment to suppress tumorigenesis. In recent years, an increasing number of new functions of p53 have been discovered, and p53-mediated tumor suppressor functions have been greatly expanded. Mutations in TP53 not only abolish its ability to suppress tumorigenesis but also confer carcinogenic properties to p53-mutant cells. Because of the prevalence of p53 dysfunction in various disease types, p53 has long been considered an attractive target for new anticancer drugs. However, drugs targeting p53 are still under investigation in early clinical trials and have not been approved for clinical use. This finding is consistent with the speculation that p53 is widely regarded as "undruggable." Surprisingly, several novel therapeutic approaches targeting p53, including MDM2/4 antagonists, compounds that target specific p53 mutants or restore the wild-type function of the mutated p53 protein, p53-based genetic therapies and p53-based tumor immunotherapy, have been developed in recent years. Here, we present a review of the structure, inactivation, and roles of p53 in diseases. In addition, this review discusses the efforts to target diseases associated with p53 dysfunction and the challenges encountered in the clinical development of these approaches.

Advanced ovarian cancer often presents with extensive pelvic and abdominal metastases, even malignant pleural effusion. Consequently, multivisceral resection has become the common surgical approach to achieve optimal resection of ovarian cancer. The present study aimed to evaluate postoperative complications and prognosis of multivisceral resection performed by the independent gynecologic oncologist team (GOT) or multidisciplinary team (MDT).

Desmoid tumors are fibroblast-derived rare soft tissue neoplasms with unclear borders that invade the surrounding structures. Despite the non-metastasizing nature, these tumors often relapse due to strong local aggressive behavior. The aim of this study was to analyze the demographic and clinical characteristics of patients with extraabdominal desmoid tumor, who underwent surgery between 2012 and 2022 and to determine the risk factors affecting recurrence.

The present study aimed to appraise the therapeutic outcomes of cystic lesion management and the diagnostic performance of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in characterizing pelvic space-occupying lesions.