ChemoNETosis represents a distinct form of therapy-induced innate immune activation, in which cytotoxic chemotherapy alters the tumor microenvironment (TME) in ways that attract and stimulate neutrophils, ultimately triggering the release of neutrophil extracellular traps (NETs). Unlike classical NETosis, which typically arises in response to infection or sterile inflammation, chemoNETosis is initiated by treatment-related danger signals and chemokine-cytokine loops that reshape the immune landscape and promote the formation of NET-rich metastatic niches. These NET structures serve not only as physical scaffolds but also as bioactive platforms enriched with proteases, reactive oxygen species, and enzymes capable of activating growth factors, collectively driving epithelial-mesenchymal transition, enhanced tumor cell plasticity, immune cell exclusion, changes in vascular permeability, and the development of chemotherapy resistance. While predominantly associated with tumor-promoting effects, chemoNETosis may, under specific genetic or metabolic conditions, contribute to antitumor responses, reflecting its context-dependent plasticity. In this review, we present what is, to our knowledge, the first in-depth synthesis of chemoNETosis across solid tumors, with a focus on key mechanistic nodes and translational perspectives.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a 5-year survival rate of 13.3%. First-line treatment relies on two chemotherapy regimens, FOLFIRINOX (FOLFNX) or gemcitabine plus nab-paclitaxel (GEMPAC). However, direct clinical comparisons between these regimens have yielded inconsistent results across survival and toxicity endpoints, and the molecular basis of heterogeneous treatment responses remains poorly defined. To investigate regimen-specific tumor-cell-intrinsic mechanisms, we performed quantitative proteomic profiling of a primary PDAC-derived MIA PaCa-2 cell line following treatment with FOLFNX or GEMPAC. Differentially expressed proteins were analyzed using Gene Ontology, KEGG, and Ingenuity Pathway Analysis to define pathway-level alterations, and findings were contextualized using TCGA transcriptomic data. Proteomic analyses revealed that FOLFNX and GEMPAC engage in distinct cytotoxic programs. FOLFNX predominantly suppressed ribosome biogenesis and mitochondrial translation, consistent with sustained metabolic and biosynthetic stress, whereas GEMPAC preferentially disrupted mitotic cytokinesis and phosphatidylinositol phosphate biosynthesis, consistent with mitotic failure. Integration with TCGA data showed that FOLFNX-altered proteins aligned with favorable prognostic expression signatures, whereas GEMPAC-associated proteins were enriched among adverse profiles, reflecting engagement of distinct tumor-intrinsic programs. Together, these findings provide mechanistic insight into differential chemotherapy responses and establish a foundation for proteomics-based biomarkers to guide personalized chemotherapy selection in PDAC.

Pancreatic cancer (PC) is a highly aggressive malignancy characterized by limited opportunities for early diagnosis and poor clinical outcomes, underscoring the need for minimally invasive biomarkers to improve detection and patient stratification. Given emerging evidence that mitochondrial DNA (mtDNA) alterations reflect cancer-related biological processes, this study investigated whether blood-derived mtDNA profiles could provide clinically relevant information in PC. In this exploratory study, whole-blood mtDNA from 33 PC patients and 10 healthy individuals were analyzed using next-generation sequencing to assess single-nucleotide variants (SNVs), allele frequencies, and mtDNA copy number. A total of 252 unique mtDNA SNVs were identified, including variants exclusive to PC patients, variants unique to controls, and variants shared between groups. While the overall SNV burden did not differ significantly between groups, PC patients showed distinct mutation distributions and allele frequency patterns, with cancer-exclusive variants occurring predominantly at low allele frequencies. Mutation hotspots were observed in the ND5, COI, and D-loop regions, implicating genes involved in oxidative phosphorylation and mtDNA maintenance. Although mtDNA copy number did not differ significantly between groups, greater variability was observed among PC patients and was associated with differences in survival outcomes. Overall, these findings indicate that blood-based mtDNA profiling captures biologically relevant variation associated with PC and supports further development of integrated mtDNA-based approaches for improved risk assessment and patient stratification.

Lamin A/C is emerging as a promising candidate regulator at the intersection of nuclear mechanics, chromatin organization, and gene regulation, linking structure and regulation, mechanics and epigenetics, constraint and plasticity. Lamin A/C was previously considered a static structural scaffold; however, it is now recognized as a dynamic component of nuclear organization that links physical cues to epigenetic and transcriptional states. Lamin A/C regulates three-dimensional genome structure, constrains chromatin mobility, and influences cell transitions between plastic and committed states through its interactions with heterochromatin at the nuclear periphery and active chromatin domains in the nuclear interior. In cancer, these functions appear to be dependent on the context. Lamin A/C has been implicated in crucial biological processes, including invasion, survival under mechanical stress, lineage plasticity, and therapeutic response. Its prognostic value varies across tumor types. This heterogeneity indicates that lamin A/C does not function as a traditional oncogene or oncosuppressor; instead, it operates as a nuclear rheostat, influencing the behavior and development of tumor cells. This review examines the potential clinical benefits of lamin A/C while considering its implications for normal tissue functions. It aims to improve understanding of cellular adaptability and vulnerability in cancer through the exploration of lamin A/C biology.

Adoptive immunotherapy using ex-vivo-amplified autologous αβ T cells has achieved notable success in the treatment of diverse cancer types. Pre-eminent among these developments has been the advent of chimeric antigen receptor (CAR) T cell therapy, which has revolutionised the treatment of selected haematological malignancies. However, autologous CAR T cell immunotherapy is poorly scalable and has demonstrated limited efficacy against solid tumours. Accordingly, there has been significant interest in alternative strategies that may bridge these gaps. The use of γδ T cells is an attractive alternative since they possess intrinsic anti-tumour activity and do not elicit graft versus host disease (GvHD) when employed as an allogeneic drug product. In this review, we evaluate the potential use of γδ T cells for cancer immunotherapy and how manufacturing and genetic engineering refinements can be used to potentiate this activity. We also summarise current clinical experience with CAR γδ T cell therapies and discuss the implications of these findings for the next generation of cellular immunotherapies.

Hepatocellular carcinoma remains one of the most common and lethal cancers worldwide, and many patients are diagnosed at stages where curative therapy is not possible. Recent progress in systemic therapies and refinements in locoregional treatment have shifted how clinicians approach this disease. As evidence has accumulated from trials such as KEYNOTE-937, IMbrave050, and CheckMate 9DX, it has become clear that pairing immunotherapy with ablation or transarterial interventions can deepen and extend treatment responses compared with using either approach alone. This review summarizes the current landscape of these combination strategies, explains the biological and clinical principles that support their use, and highlights ongoing trials that aim to clarify optimal sequencing and patient selection. It also considers future directions for integrating locoregional and systemic therapies to expand curative opportunities and improve long-term outcomes for a broader range of patients.

Prostate cancer (PCa) remains a major global health challenge, yet conventional diagnostic methods are often limited by suboptimal accuracy and efficiency. Artificial intelligence (AI) has emerged as a rapidly developing technology capable of integrating multi-source data to enhance clinical decision-making. This narrative review synthesizes current evidence regarding AI applications across key diagnostic domains, including medical imaging, digital pathology, liquid biopsy, and multi-omics integration. Findings indicate that AI models for magnetic resonance imaging (MRI) can improve risk stratification and may reduce unnecessary biopsies in some cohorts, particularly when evaluated alongside structured radiology assessment and clinical variables. In digital pathology, deep learning algorithms have shown high agreement with expert genitourinary pathologists for automated Gleason grading in controlled and externally validated settings, with potential to reduce reporting time for high-volume workflows. Additionally, AI-powered liquid biopsy models may support non-invasive risk stratification, particularly for patients with prostate-specific antigen (PSA) levels in the diagnostic gray zone, while multi-omics integration is being investigated to enhance personalized assessment. Despite advances, challenges regarding data heterogeneity, algorithm interpretability, and workflow integration persist. Future research should prioritize multimodal data fusion, explainable AI development, robust calibration and decision-analytic evaluation, and large-scale prospective validation to standardize protocols and fully realize the potential of AI in precision prostate cancer care.

From an epidemiological perspective, polymorphous low-grade neuroepithelial tumor (PLNTY) represents a small proportion of brain tumors encountered in epilepsy surgery series. Their rarity and relatively recent recognition likely contribute to underdiagnosis and poor prognosis. In terms of histopathological features, they are similar to oligodendrogliomas. Molecular analyses can be used to show the fusion between fibroblast growth factor receptor (FGFR3) and transforming acidic coiled coil (TACC) proteins, which most commonly results in progression towards glioblastoma (GBM). We report a case of a 62-year-old man who underwent left frontal craniotomy to remove a frontal mass. Histologically, the glial lesion consisted of elements associated with oligodendroglia-like features. Immunohistochemistry was positive for glial fibrillary acidic protein (GFAP), oligodendrocyte transcription factor 2 (OLIG2), and α-thalassemia X-linked mental retardation syndrome (ATRX) nuclear expression, but negative for isocitrate dehydrogenase 1 (IDH1) and BRAF-V600E. Next-generation sequencing showed the FGFR-TACC3 fusion, and taken together, these findings supported the final diagnosis of PLNTY. During follow-up, the patient underwent a second neurosurgery, where histological evaluation indicated a GMB. This article presents clinical and radiological data, morphology, immunohistochemistry, molecular features, and treatment to enhance the clinical and pathological understanding of PLNTY with FGFR3-TACC3 fusion for all professionals involved in medical decisions.

Immune checkpoint inhibitors and antibody drug conjugate combinations have revolutionized the management of patients with advanced and metastatic urothelial carcinoma, offering unprecedented survival outcomes. These treatments are now moving into earlier stages of disease, including perioperative treatments for patients with muscle-invasive bladder cancer planning for curative-intent radical cystectomy. In this setting, there are now standard-of-care options for adjuvant immune checkpoint inhibitors with or without prior neoadjuvant chemotherapy, perioperative immune checkpoint plus cytotoxic chemotherapy combinations, and perioperative immune checkpoint inhibitor plus antibody drug conjugate combinations. This review will evaluate key clinical trials that led to modern standards of care involving these classes of drugs and highlight ongoing clinical trials that may further shift treatment paradigms for muscle-invasive bladder cancer. Key efficacy and toxicity considerations will be reviewed, and available evidence for biomarkers will be evaluated. As immune checkpoint inhibitors and antibody drug conjugates continue to demonstrate improved outcomes across the spectrum of bladder cancer treatment, understanding their role in the muscle-invasive disease state is crucial to managing patients with this condition.

Fluorescence-guided surgery based on near-infrared imaging, most often using indocyanine green (ICG), is increasingly used in colorectal cancer (CRC) surgery. This narrative review integrates current evidence across four clinically relevant domains-anastomotic perfusion, lymphatic mapping, tumor localization, and metastasis detection and emphasizes the technical and translational factors that will determine broader implementation.

We performed a structured narrative review of clinical and translational studies identified through PubMed and citation tracking, with emphasis on ICG-based workflows and emerging targeted tracers. Because the literature spans heterogeneous interventions, imaging platforms, and endpoints, no de novo meta-analysis or formal risk-of-bias assessment was undertaken.

ICG fluorescence angiography is the most mature application and can refine transection-line selection, although its effect on anastomotic leak appears protocol dependent. In lymphatic mapping, ICG improves visualization of drainage pathways and nodal basins but does not reliably distinguish benign from metastatic nodes. For tumor localization, ICG supports lesion marking and dynamic tissue characterization, while targeted probes and contrast-free adjuncts may improve oncologic specificity. For metastatic disease, ICG is most useful for liver margin guidance and for excluding residual disease, whereas CEA-targeted and multimodal approaches appear particularly promising for peritoneal metastases.

The added value of this review lies in linking current clinical maturity to the translational steps still required for routine adoption. In CRC surgery, fluorescence imaging is already useful in selected settings, but broader implementation will depend on standardized protocols, objective real-time quantification, and multicenter validation of targeted tracers against clinically meaningful outcomes.