Background/Objectives: Primary renal NETs are exceptionally rare neoplasms that occur disproportionately in horseshoe kidneys. Their rarity and non-specific clinical and radiological features make preoperative diagnosis particularly challenging. Methods: Herein, we report the case of a 60-year-old woman presenting with a painful left lumbar mass associated with dysuria and pollakiuria. Results: Computed tomography revealed a large heterogeneous tumor arising from the left moiety of a horseshoe kidney. Histopathological examination of the resected specimen demonstrated a 14 cm well-differentiated NET (grade 1) with diffuse chromogranin A and synaptophysin expression, a mitotic count of 1 per 2 mm2, and a Ki-67 proliferation index of <1%. The histopathological and immunohistochemical findings, together with the absence of an extrarenal primary site on staging investigations, supported the diagnosis of a primary renal NET. The postoperative course was uneventful, and the patient remained disease-free after two years of follow-up. Conclusions: This case highlights the diagnostic challenges posed by this rare entity and underscores the importance of including primary renal neuroendocrine tumors in the differential diagnosis of renal masses arising in horseshoe kidneys.
Head and neck squamous cell carcinoma (HNSCC) remains a significant global health burden with limited survival improvement in locally advanced disease despite multimodal therapy. Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 pathway have demonstrated substantial clinical benefit in recurrent or metastatic HNSCC, establishing PD-1 blockade as a standard of care. Similar approaches in locally advanced disease, including concurrent administration with chemoradiotherapy or use in the adjuvant setting, have not demonstrated improvement in survival outcomes across multiple randomized trials. Perioperative strategies incorporating neoadjuvant and adjuvant checkpoint inhibition have shown improved event-free and disease-free survival in resectable disease. Meta-analyses of concurrent and adjuvant approaches confirm limited benefit in unselected populations, with modest improvements restricted to biologically defined subgroups. Trial outcomes across disease settings demonstrate a consistent pattern in which therapeutic efficacy varies despite the use of similar agents. Rather than simply summarizing these clinical findings, this review integrates evidence across recurrent/metatstatic, unresected locally advanced and perioperative disease settings into a biologically focused framework to help explain the varying efficacies of immune checkpoint inhibition in HNSCC. Current evidence indicates that the effectiveness of immunotherapy in HNSCC is determined by the biologic context of treatment, including tumor antigen availability, host immune competence, and timing of immune activation. Administration of checkpoint blockade in the presence of intact tumor antigen and preserved immune function is associated with improved outcomes, whereas treatment delivered during or after cytotoxic therapy is limited by lymphopenia and reduced antigen exposure. By synthesizing randomized clinical evidence through this biologic framework, the review provides a conceptual perspective that may help explain previous trial outcomes and inform future biomarker-driven patient selection and treatment sequencing. Optimization of immunotherapy in HNSCC will depend on the integration of immune activation with disease context rather than an escalation of therapeutic intensity.
(1) Background: Modifications to tumor classifications could fundamentally alter the foundation of the research approaches. A concrete illustration of this issue is the actual WHO classification of tumors of the central nervous system, published in 2021. According to the WHO classification, a GBM must be IDH wild-type. However, some multi-omics databases retain the classification from the time the samples for the datasets were collected, prior to the WHO 2021 classification, including IDH-mutant GBMs. We were interested in assessing the number of papers published in the biomedical literature from 2022 to 2025 that are based on these databases, to ensure the correct implementation of the WHO 2021 classification of GBM. (2) Methods: We systematically reviewed publications in the biomedical literature from 2022 through 2025 that utilized the two most widely used multi-omics databases in the glioma research field, the CGGA and TCGA databases, to assess the correct application of the classification of GBM. (3) Results: We identified 182 publications, but only 26 (14%) correctly included only IDH wild-type GBM; 61 (33%) also contained IDH mutant tumors, and 93 (53%) provided no information about the IDH status of their research material. (4) Conclusions: Using a systematic search strategy, we found that 1/3 of published papers used IDH mutant tumors, and 1/2 of the studies did not report the IDH status of the tumors.
Obesity is increasingly recognized as a complex systemic disorder rather than a simple consequence of excess energy intake and fat accumulation. This review presents a systems biology framework that examines how obesity-driven disruption of inter-organ communication networks contributes to chronic disease susceptibility, with particular emphasis on colorectal cancer (CRC). Disrupted signaling among the brain, adipose tissue, liver, skeletal muscle, gut, and immune system generates maladaptive feedback loops that promote chronic metabolic inflammation (metaflammation), loss of physiological resilience, and progressive metabolic dysfunction. Within this framework, obesity is redefined as a network disease characterized by neuroendocrine dysregulation, adipose tissue remodeling, immune dysfunction, impaired organ crosstalk, and alterations in the gut microbiome. A central feature of this dysregulation is persistent low-grade inflammation driven by immune-metabolic reprogramming and sustained activation of inflammatory pathways. Obesity-associated metaflammation is further linked to accelerated biological aging through mechanisms involving cellular senescence, mitochondrial dysfunction, oxidative stress, and impaired metabolic resilience. These interconnected processes create a tumor-promoting environment by enhancing oncogenic signaling, disrupting intestinal barrier integrity, altering microbial and metabolic signaling, impairing immune surveillance, and promoting epithelial dysfunction, thereby increasing susceptibility to CRC. The review also examines how behavioral, circadian, environmental, and socioeconomic factors influence metabolic health and cancer risk. Finally, emerging translational opportunities, including biomarker-guided risk stratification, precision prevention, metabolic network restoration, and integrative lifestyle and pharmacological interventions, are discussed. Collectively, this review reframes obesity as a whole-body regulatory disorder and provides an integrated conceptual framework linking metabolism, inflammation, aging, and colorectal carcinogenesis to inform future prevention and therapeutic strategies.
Metastatic castration-resistant prostate cancer (mCRPC) is a prevalent malignancy marked by molecular heterogeneity, which contributes to resistance to standard therapies and poor clinical prognosis. Advances in genomic and transcriptomic profiling have identified key drivers such as alterations in AR, TP53, PTEN, and RB1, which also enable cancer cells to circumvent therapies. Despite such advances, the underlying mechanisms involved in mCRPC drug resistance are complex, creating an urgent need for novel therapies to improve clinical outcomes. To address this clinical problem, strategies focused on targeting underlying molecular and metabolic supportive pathways using nano-delivery systems of diverse drugs could be promising in both CRPC and mCRPC therapy. This review provides an overview of the current understanding of the genomic and microenvironmental landscape of mCRPC and explores emerging classification frameworks aimed at improving patient outcomes. We highlight the potential of integrative multi-omics approaches to inform precision oncology and guide the development of more effective, personalized treatments for prostate cancer therapy.
Oral cancer remains a major global health problem with high morbidity and mortality rates, and despite advances in therapeutic approaches, challenges persist in early diagnosis and effective disease management. MicroRNAs (miRNAs) are endogenous, small non-coding RNAs that regulate gene expression at the post-transcriptional level and play fundamental roles in maintaining cellular homeostasis, as well as in the initiation and progression of multiple malignancies, including oral cancer. Dysregulation of miRNAs contributes to oral carcinogenesis by modulating key cellular processes such as cell proliferation, apoptosis, invasion, metastasis, and angiogenesis. Altered miRNA expression profiles have been consistently identified in oral cancer tissues and body fluids, including saliva and blood, supporting their potential utility as reliable biomarkers for early detection, prognosis, and disease monitoring. Circulating miRNAs, in particular, represent a promising non-invasive diagnostic tool for assessing disease progression and therapeutic response. Moreover, miRNAs are actively involved in regulating sensitivity and resistance to chemotherapy and radiotherapy, with specific miRNAs either enhancing treatment efficacy or promoting therapeutic resistance. This review aims to highlight the critical role of miRNAs in oral cancer pathogenesis, diagnosis, prognosis, and treatment, exploring their potential as biomarkers and therapeutic targets to improve early detection, patient outcomes, and personalized treatment strategies.
In cancer biology, the microbiome has emerged as a revolutionary field, revealing host–microbe interactions that drive cancer initiation, development, metastasis, and therapeutic response. The microbiome plays a mechanistic role in carcinogenesis by directly regulating host cell proliferation, apoptosis, and genomic stability, and indirectly through immune regulation and chronic inflammation. Depending on the microbial genetic makeup and host environment, microbial genotoxins, metabolites, and signaling molecules can either induce tumor growth or exert beneficial anticancer effects. Infectious agents are estimated to trigger a significant proportion of cancers globally, although the mechanistic pathways of the broader microbiome remain less well quantified. Likewise, it has been shown that microbiomes modulate the toxicity and efficacy of cancer treatments—specifically immunotherapy and chemotherapy—by mediating anti-tumor reactions and altering drug metabolism. Microbiome-based diagnostics, predictive markers, and therapeutic strategies like dietary modifications, probiotics, synthetic microbes, and fecal microbiota transplantation have collectively benefited from these breakthroughs. Despite rapid progress, integrating microbiome research into oncology is hindered by patient variability, methodological hurdles, and the difficulty of identifying definitive causal links. Large-scale clinical trials are essential for verifying the functional impact of microbiome-targeted treatments. The current review evaluates the mechanistic influence of microbiomes on cancer diagnosis and therapeutics.
Colorectal cancer (CRC) is a major worldwide health concern and a leading cause of cancer-related mortality, with over 1 [...]
Background/Objectives: Pelvic radiotherapy (RT) for mid–low rectal and anal cancers frequently causes acute and late vaginal toxicity, including dryness, irritation, and dyspareunia, with a substantial impact on quality of life. Evidence supporting targeted interventions for radiation-induced vaginal mucosal changes remains limited. This exploratory retrospective study evaluated the association between daily use of Colpofix® Ovules and temporal changes in patient-reported vaginal symptoms and Vaginal Health Index (VHI) scores in women undergoing pelvic RT. Methods: Twenty women treated with pelvic RT or chemoradiotherapy between 2024 and 2025 were included. Vaginal symptoms were assessed using a Numerical Rating Scale (NRS 0–10), and mucosal status was evaluated using the VHI (5–25). Assessments were performed at baseline (T0), end of RT (T1), 3 months (T2), and 6 months (T3). Due to the retrospective nature of the dataset, only aggregated summary values were available; analyses were therefore descriptive and aimed at characterizing temporal trends. Results: A clear and progressive reduction in vaginal dryness, irritation, reduced lubrication, and dyspareunia was observed from T0 to T3, with improvements already evident at T1 and further consolidation at T2–T3. VHI scores increased from a mean of 10.8 at baseline to 21.0 at 6 months, reflecting a consistent trend toward mucosal recovery across all domains. In the anal cancer subgroup, the trend toward improvement in dysuria did not meet conventional thresholds for statistical significance (p = 0.073). At T3, 90% of patients reported perceived benefit (55% marked, 35% mild). No adverse events attributable to Colpofix® were documented. Conclusions: In this small retrospective cohort, daily use of Colpofix® Ovules was associated with favorable temporal trends in both vaginal symptoms and VHI scores up to 6 months after pelvic RT. These exploratory findings support further prospective controlled studies to better define the potential role of Colpofix® in managing vaginal mucosal changes during pelvic radiotherapy.
Background: Current murine glioblastoma (GBM) models do not incorporate tumor resection and thus do not allow study of recurrent GBM after surgery, including postsurgical changes in the tumor microenvironment (TME), thereby limiting translational relevance. Methods: In phase 1 of a three-phase study, we compared tumor cell implantation into a cavity created using conventional microdissection techniques or the Myriad Research Laboratory System (MRLS) versus direct implantation into the brain without a cavity, and assessed morbidity using the neurological severity score (NSS). In phase 2, we developed a new surgical resection model, the Surgical murine GBM resection model (Sur-rGBM), and examined the effects of tumor resection on the tumor microenvironment (TME) and on overall survival. In phase 3, we compared the therapeutic response to temozolomide (TMZ) with or without anti-VEGF antibody, after resection (Sur-rGBM) or no resection. Tumor growth was confirmed before and after resection by ultrasound. Animals were euthanized for immunohistochemical assessment at maximal tumor growth. Results: Creating a cavity for tumor cell implantation using MRLS improved survival compared to direct cell injection with no cavity. Tumor resection increased survival, and TMZ combined with an anti-VEGF antibody after tumor resection improved survival compared with surgery or TMZ alone. Resection induced significant changes in biomarker expression within the TME. Conclusions: Our novel murine GBM surgical resection model (Sur-rGBM) provides reliable, controlled tumor growth and a standardized resection technique to facilitate studies on TME changes and therapeutic response after tumor resection.
Intercellular mitochondrial trafficking has emerged as an important mechanism influencing tumor progression, metabolic adaptability, and cancer cell plasticity. Beyond their classical bioenergetic functions, mitochondria act as central regulators of redox homeostasis, signaling pathways, and epigenetic remodeling. Increasing evidence suggests that mitochondria can be transferred between tumor, stromal, and immune cells through tunneling nanotubes (TNTs), extracellular vesicles (EVs), gap junctions, and cell fusion within the tumor microenvironment. This dynamic excshange enables metabolically compromised cancer cells to restore oxidative phosphorylation, optimize energy production, and survive under hypoxia and therapeutic stress. Mitochondrial transfer has been increasingly associated with enhanced cellular plasticity and adaptive phenotypic transitions, including the acquisition of stem-like features that contribute to tumor heterogeneity, metastasis, and treatment resistance. In addition to bioenergetic restoration, transferred mitochondrial DNA and metabolites participate in retrograde signaling, linking metabolic state to epigenetic regulation and transcriptional reprogramming. This metabolic epigenetic interplay supports tumor cell adaptation to environmental stress and therapeutic pressure. Although significant progress has been made, the precise mechanisms governing mitochondrial integration and their long-term impact on cellular phenotypes remain incompletely understood. A deeper understanding of these processes may reveal novel therapeutic strategies to disrupt tumor adaptability and progression. Specifically, targeting intercellular mitochondrial trafficking and its associated metabolic and epigenetic effects could help limit tumor plasticity, overcome treatment resistance, reduce disease recurrence, and improve overall clinical outcomes in cancer patients.
Background/Objectives: In Puerto Rico (PR), lung cancer mortality remains high because diagnoses frequently occur at advanced stages. Although low-dose computed tomography (LDCT) lowers lung cancer–specific mortality, this screening is difficult to operationalize locally due to high false-positive rates, radiology capacity constraints, payer limitations, and geographic barriers affecting rural populations. Methods: We performed a narrative review on the literature from 2001–2026 of established and emerging detection strategies—LDCT; serum biomarkers (CEA, CYFRA-21-1, NSE, ProGRP, SCC-Ag, HE4, Hp, TAAb); breath analysis (FeNO and VOCs); and liquid biopsy (ctDNAs/CTCs/miRNAs). We assessed technical performance, feasibility, and health-system fit in PR and then synthesized these findings into an implementable biomarker-first triage workflow for are. Results: Multiplex serum panels analyzed with machine learning outperform single markers and TAAb provide high specificity with biological lead time, supporting their use as a triage gateway before LDCT. Breathomics is also feasible at the point of care. Liquid biopsy has modest sensitivity in very-early disease yet provides molecular adjudication for indeterminate nodules. A stepwise pathway—expanded risk assessment, integrated multi-panel testing in primary care, LDCT reserved for biomarker-positive individuals, and liquid biopsy when imaging is inconclusive—can enrich pre-test probability, reduce unnecessary scans, align with capitation, and protect limited radiology capacity. Conclusions: An integrated, non-invasive, biomarker-first triage model offers a pragmatic, equitable route to earlier lung cancer detection in PR and resource stewardship, while reducing disparities.
Immunotherapy with immune checkpoint inhibitors (ICIs) has profoundly transformed the therapeutic landscape of lung cancer. Although ICIs are generally associated with a more favorable toxicity profile compared with traditional chemotherapy, rare and potentially severe immune-related adverse events (irAEs) may occur, sometimes posing significant diagnostic challenges. We report a case of macrophage activation syndrome (MAS) following a single administration of the anti-PD-L1 antibody atezolizumab in a patient with advanced non-small-cell lung cancer (NSCLC). A 62-year-old woman was diagnosed in February 2024 with stage IIIB NSCLC according to the 8th TNM classification. The patient was deemed ineligible for radiotherapy because of previous thoracic irradiation for breast cancer. First-line therapy with carboplatin plus pemetrexed was administered from March to June 2024, resulting in stable disease; this was followed by pemetrexed maintenance from July to October 2024, at which time thoracic disease progression was documented. Second-line treatment with atezolizumab was initiated in November 2024. Ten days after the first infusion, the patient was admitted to the emergency department for fever and confusion. Laboratory investigations revealed markedly elevated C-reactive protein and hyperferritinemia. Despite empirical antibiotic therapy, fever and thrombocytopenia persisted. Bone marrow biopsy demonstrated findings consistent with MAS. Corticosteroid therapy with prednisone at 1 mg/kg was promptly initiated under rheumatologic supervision, leading to a rapid clinical and biochemical improvement. During tapering, inflammatory markers relapsed when prednisone was reduced to below 12.5 mg/day. Given the occurrence of a grade 4 (CTCAE v5.0) immune-related adverse event, atezolizumab was permanently discontinued. The patient remains in follow-up without radiological evidence of disease progression. This case highlights the diagnostic challenge of MAS secondary to ICIs, which may initially present with nonspecific symptoms such as fever, confusion, and elevated inflammatory markers. Early recognition and timely initiation of high-dose corticosteroids were essential for effective management and full recovery. Clinicians should maintain a high index of suspicion for MAS among rare but severe hematologic irAEs during immunotherapy.
Background: Muscle-invasive bladder cancer (MIBC) is an aggressive disease with heterogeneous responses to neoadjuvant chemotherapy and emerging chemo-immunotherapy combinations. Reliable biomarkers to predict treatment responsiveness before therapy initiation are needed to guide patient selection. Objective: The objective of this study was to identify genomic and immune-related features associated with immune-active tumor phenotypes in MIBC using The Cancer Genome Atlas bladder cancer cohort (TCGA-BLCA). Methods: A retrospective bioinformatics analysis of TCGA-BLCA data was performed, evaluating gene expression, somatic mutations, tumor mutational burden (TMB), DNA damage response (DDR) gene status, and immune infiltration signatures. Immune enrichment metrics were derived from transcriptomic data. In the absence of direct treatment response data, a surrogate immune response classification was applied. Associations were analyzed using descriptive statistics and Firth’s penalized logistic regression. Results: Tumors classified as immune-high phenotype group based on immune-related features exhibited significantly higher global immune infiltration, including increased ImmuneScore and enrichment of cytotoxic and innate immune cells. In multivariable analysis, ImmuneScore was the only independent predictor of inferred responsiveness (p = 0.003). Conclusions: Global immune infiltration showed the strongest association with immune-active tumor phenotypes among the features examined in this TCGA-based analysis. These exploratory findings suggest that immune profiling may warrant further investigation as a component of tumor characterization in MIBC, pending validation in cohorts with clinical treatment and outcome data.
The family of uterine mesenchymal neoplasms is diverse in etiology and clinical impact. While histomorphology remains central to diagnostic classification, numerous biomarkers have been developed to aid in refining diagnoses and informing optimal treatment strategies. Indeed, a growing number of neoplasms are being primarily classified on the basis of key pathognomonic genetic events, and this number is expected to continue expanding as access to next-generation sequencing rapidly democratizes. Moreover, several quantitative biomarker tests have been developed to aid in the prognostic stratification of tumours with ambiguous morphologic features, providing critical insights to clinicians seeking optimal oncologic management while minimizing unnecessary treatment morbidity. In this review, we discuss key advances in the utilization of biomarkers for diagnostic classification, prognostication, and the prediction of response to targeted therapeutics in uterine mesenchymal neoplasms, with the aim of highlighting the most clinically impactful biomarkers used by pathologists to enhance the clinical care of patients.
Background/Objectives: Brain tumors, particularly gliomas, have high mortality and are limited in treatment options, often complicated by severe conditions, which can be fatal. Given the increasing incidence and adverse effects of current drugs, an in silico drug repurposing approach using hub gene clusters to streamline and accelerate the search for new therapies. Methods: The GSE66354, GSE68848, GSE74195, and GSE43290 datasets were used to identify DEGs using GEO2R. A gene co-expression network was constructed using the STRING PPI database. Preserved clusters revealed hub genes, which were used for GO and KEGG pathway enrichment analyses. Drug repurposing screening was performed through drug–gene interactions in DGIdb. Suggestive drugs were then validated through GSEA-CMAP and BOILED-Egg. Results: The study identified three key gene clusters that serve a role in synaptic transmission and transmembrane transport, synaptic vesicle neurotransmission, and extracellular matrix formation. Five drugs passed the drug screening, which are Gabapentin, Pyrantel, Resveratrol, Trifluoperazine, and Valproic acid. Conclusions: Valproic acid and Gabapentin are highly suggestive as candidate repurposed drugs. This study enhances our understanding of brain tumor genetics and supports the development of new immunotherapeutic strategies.
Background: There are approximately 5.4 M basal cell (BCC) and squamous cell (SCC) carcinomas diagnosed each year, and the number is increasing. Currently, the gold standard for skin cancer diagnosis is histopathology, which requires the surgical excision of the tumor followed by pathological evaluation of a tissue biopsy. The three-dimensional (3D) nature of human tissue suggests that two-dimensional (2D) cross sections may be insufficient in some cases to represent the complex structure due to sampling bias. There is a need for new techniques that can be used to classify skin lesion types and margins noninvasively. Methods: We use optical coherence tomography volume scan images and AI to noninvasively create 3D images of basal cell and squamous cell carcinomas. Results: Three-dimensional optical coherence tomography images can be broken down into a series of cross sections that can be classified as benign or cancerous using convolutional neural network models developed in this study. These models can identify cancerous regions as well as clear edges. Cancerous regions can also be verified based on visual review of the color-coded images and the loss of the green and blue subchannel pixel intensities. Conclusions: Three-dimensional optical coherence tomography cross sections of cancerous lesions can be collected noninvasively, and AI can be used to classify skin lesions and detect clear lesion edges. These images may provide a means to speed up treatment and promote better patient screening, especially in older patients who will likely develop several lesions as they age.
Objectives. Pancreatic cancer remains one of the most lethal malignancies, and the lack of effective therapies highlights the need for novel treatment strategies. In this study, we evaluated the antitumor potential of the attenuated Streptococcus pyogenes strain GURSA1—engineered to knockout the M protein completely—in a murine model of orthotopically transplanted pancreatic ductal adenocarcinoma. Methods. Female C57Bl/6 mice received intratumoral injections of GURSA1 at doses of 5 × 105 or 1 × 106 CFU per animal. Animal survival, body weight, tumor engraftment, metastasis intensity, tumor mass and volume, and hematological, biochemical, histological, and microbiological parameters were assessed. Results. Intratumoral administration of GURSA1 produced dose-dependent antitumor effects on tumor growth and metastatic burden, but did not result in a statistically significant survival benefit. The strain reduced tumor engraftment, the overall metastasis score, and the incidence of hemorrhagic ascites, while also decreasing tumor mass and volume, with the strongest effects observed at a dose of 1 × 106 CFU. Treatment increased platelet counts and reduced urea and ALT levels toward values observed in intact mice, without affecting anemia, neutrophilia, or changes in AST, alkaline phosphatase, glucose, and total protein levels. Conclusions. These findings demonstrate that GURSA1 attenuates partial reduction in primary tumor burden in vivo and support further investigation of this strain as a potential oncolytic agent.
Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine disease marked by rapid growth, early metastatic spread, and poor outcomes. The addition of immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis to first-line chemotherapy has recently reshaped the treatment landscape for extensive-stage SCLC (ES-SCLC); however, the resulting survival gains remain modest compared with non-small lung cancer (NSCLC). This review explores the molecular features of the SCLC immune landscape that contribute to its predominantly “cold” tumor phenotype, including low MHC class I expression, T-cell exhaustion, and a profoundly immunosuppressive tumor microenvironment (TME). We summarize key clinical findings from landmark trials and examine mechanisms of both primary and acquired resistance against ICIs in SCLC. In addition, we have reviewed the growing role of precision medicine in SCLC, including molecular subtyping (SCLC-A, -N, -P, and -I) and the development of next-generation immunotherapies such as bispecific T-cell engagers (BiTEs), B7-H3, targeted therapy, and antibody–drug conjugates. By combining existing clinical evidence with new molecular insights, this review article presents strategies to overcome the existing therapeutic plateau and enhance personalized immunotherapy approaches in SCLC.
