Treatment of locally advanced and metastatic prostate cancer (PC) with androgen receptor-targeting (AR-targeting) therapies has limited durability, with disease eventually progressing to castrate-resistant PC (CRPC). Constitutively active AR splice variants (AR-Vs), such as AR-V7, play a key role in driving treatment resistance and disease progression. Importantly, the failure to attenuate AR-V function represents a major unmet clinical need, and as such, defining how AR-Vs are generated is likely to yield new therapeutic targets. Our knowledge of factors that mediate splicing of AR-V-encoding mRNAs remains limited. Here, we have employed an RNA-targeting CasRx approach to identify selective protein interactors of AR-V7 mRNA in PC. TRA2B and its ortholog, TRA2A, were identified as splicing regulators of AR transcripts that facilitate AR-V synthesis at the expense of full-length AR isoforms. TRA2B expression correlated with AR-V7 transcript in CRPC and attenuation of TRA2-mediated splicing diminished PC cell growth. Exploiting TRA2B function may therefore provide new therapeutic opportunities in advanced disease.

The role of intensity-modulated radiotherapy (IMRT) and novel combination chemotherapy regimens in locally advanced pancreatic cancer (LAPC) remains unclear. In this study, we focused on comparing survival between first-line chemotherapy alone and first-line chemotherapy plus IMRT in patients with LAPC.

The progression from cirrhosis to hepatocellular carcinoma (HCC) is a key outcome in the management of chronic liver disease. This process has a long incubation period and significant individual differences, making early warning still difficult. Clinical follow-up mainly relies on imaging examinations and alpha fetoprotein, but the ability to identify high risk precancerous states is limited. The imbalance of gut microbiota and its metabolites may occur earlier than the visible stage of tumors. They can affect barrier integrity, chronic inflammation, immune surveillance, and metabolic homeostasis through the gut liver axis, and participate in the formation of a pro tumor microenvironment. Therefore, such changes may provide more upstream risk stratification clues for the population with cirrhosis. This article summarizes previous research evidence and summarizes the common microbiome and metabolite characteristics of cirrhosis and high-risk populations, including a decrease in short chain fatty acid (SCFA) related symbiotic bacteria, an increase in inflammation related bacteria, bile acid spectrum shift, and other intestinal derived metabolite abnormalities. This article also outlines the key mechanisms that these features may correspond to, such as barrier damage and microbial translocation, immune suppression, etc. There are still significant uncertainties at present. The effect of SCFA is context dependent. Different etiologies, diets, medications, and complications can lead to significant confounding and affect cross cohort consistency. Subsequent research requires longitudinal cohort validation and the promotion of multi omics integration and the construction of interpretable predictive models to support clinical translation.

To evaluate the effectiveness of different methods for segmenting tumor regions of interest in building prediction models for the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade of clear cell renal cell carcinoma (ccRCC).

Familial adenomatous polyposis (FAP) is characterized by hundreds of colorectal adenomas that inevitably progress into carcinomas. This study focused on the heterogeneity during the polyposis progression to identify new targets and signatures for therapeutic development.

Local radiotherapy rarely triggers regression of distant, non-irradiated tumors (the "abscopal" effect), but this outcome is unpredictable because it depends on interacting processes, such as antigen release, antigen presentation, T-cell priming and trafficking, and lymphoid health. To study these interactions quantitatively and identify dominant mechanisms that control off-target tumor responses, we built an integrated physiologically based pharmacokinetic - quantitative systems pharmacology (PBPK-QSP) model.

Tumor cells frequently develop immune resistance through interferon-γ (IFN-γ)-induced PD-L1 expression, acquisition of cancer stem cell (CSC)-like features, and adaptation to hypoxia within the tumor microenvironment (TME). Although IFN-γ activates both STAT1 and STAT3, how these pathways interact to regulate immune evasion under hypoxia remains unclear.

Tumor-associated macrophages (TAMs) are a highly heterogeneous population of innate immune cells that is widely enriched in the tumor microenvironment (TME). By suppressing anti-cancer immunity, TAMs sustain tumor growth, metastasis development and contribute to therapy resistance. Due to their remarkable plasticity, TAMs can be reprogrammed towards immune-stimulatory phenotypes, representing a compelling therapeutic option. The mitochondrial electron transport chain (ETC) is central in fueling macrophage metabolism by coupling electron flow with proton transfer to produce Adenosine Triphosphate (ATP). During inflammation, remodeling of the ETC has been shown to regulate macrophage polarization and cytokine production. However, how ETC perturbations influence macrophage phenotypes in other diseases, as during cancer progression and within a nutrient-restricted environment remains largely unexplored. In this mini-review, we examine the role of the ETC and its individual respiratory complexes in governing tumor-associated macrophage behavior, their involvement in tumor immunity, and we discuss the potential to exploit this axis for innovative immunotherapeutic strategies, while also considering current challenges and limitations.

Chronic viral infections, such as HBV, HCV, EBV, and HPV, contribute to tumorigenesis not only through direct oncogenic effects but also by reshaping the tumor immune microenvironment (TIME) via complex immunoregulatory mechanisms. These infections enhance immune suppression and promote metastasis. Viruses induce the accumulation of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and immunosuppressive cytokines, while driving CD8+ T cell exhaustion and impairing NK cell function, creating an immune environment favorable for tumor survival. Chronic inflammation, pro-angiogenic factors, and signals mediated by exosomes and microvesicles further remodel local and distant microenvironments, forming a "pre-metastatic niche" that supports tumor cell colonization and metastasis. Key signaling pathways, including NF-κB, STAT3, PD-1/PD-L1, and TGF-β, are persistently activated by viral proteins such as HBx and LMP1, reinforcing immunosuppression and metastasis. Based on these mechanisms, combined strategies of antiviral therapy with immune checkpoint inhibitors (ICIs) or targeting exosomes and immunosuppressive pathways show potential to enhance antitumor immunity and limit metastasis. A deeper understanding of the virus-immune-metastasis axis and related biomarkers may provide precise immunotherapeutic strategies for virus-associated cancers and improve patient outcomes.

The emergence of tumor cell resistance is one of the major issues in current oncology practice. It reduces the effectiveness of therapy and worsens cancer patients' prognoses. However, it confirms a wide range of molecular interactions as well as the complexity of the human organism. Our previous research confirmed the functionality of the erythropoietin receptor (EPOR) in ovarian and breast cancer cells, as well as its relationship to these cells' sensitivity to specific therapies. The current study demonstrates that EPOR overexpression in human ovarian adenocarcinoma cells A2780 is directly linked to paclitaxel resistance. Furthermore, EPOR overexpression results in morphological changes that vary according to the pattern of EPOR isotypes expressed. In this regard, the most interesting result appears to be the change in the shape of the T clone, which has a tendency to form spheroidal structures. In addition, functional enrichment analysis demonstrated that EPOR-associated differentially expressed genes are involved in several biological and cell processes. Indeed, a T clone with a single 68 kDa EPOR isotype demonstrates significant resistance to paclitaxel therapy and is associated with the upregulation of tubulin beta 6.

Recently, stool- and blood-based cancer screening kits have been approved in clinical practice as convenient and noninvasive methods for colon cancer screening. One such test in long-standing practice has included the fecal immunochemical test (FIT), wherein home-based testing has rendered it a convenient initial assay to complement screening colonoscopy, despite limitations in diagnostic performance. In a recent original study published in the journal by Nguyen and colleagues, the feasibility and performance of combining FIT with circulating tumor cell (CTC) enumeration for predicting colorectal neoplasia and the risk of developing colorectal cancer were described. In this commentary, we highlight the potential of this combination as a novel colorectal cancer screening technique. The introduction of CTC as a potential colorectal cancer screening assay is timely, given the emergence of liquid biopsies that hold promise in their ability to detect a multitude of cancer-specific signals, from the detection of minimal residual disease to the detection of molecular alterations for precision therapies in oncology. We place the importance of their results in the context of the evolving landscape of stool- and blood-based colorectal cancer screening tests involving multitarget fecal DNA and cell-free DNA assays. See related article by Nguyen et al., Cancer Epidemiol Biomarkers Prev 2026;35:79-87.

Cancer cells can repurpose a fundamental bone development program to escape therapy in a dormant state. This finding offers a way to detect cancer dormancy and assess recurrence risk using routine bone scans. See related article by Sreekumar et al., p. 781.

Metastasis is a multiorgan disease in which disseminated cancer cells undergo profound, tissue-specific reprogramming that reshapes their identity, vulnerabilities, and therapeutic responses. We argue for an organ-informed precision oncology framework that integrates these site-imposed programs into treatment design.

We propose a physics-based framework in which cancer cell state is defined by position and velocity in a continuous space of directly measurable physical variables-cell surface area (S) and volume (V)-and motion through S-V space as an interpretable proxy for plasticity. Therapy generates S-V vector fields that govern trajectories, enabling the design of drug combinations to steer heterogeneous cell populations toward nonviable states, offering a predictive and physically interpretable alternative to therapies directed against oncogenic mutations and/or predefined cell subpopulations.

Anterior mediastinal tumors, involving structures such as the thymus and lymph nodes, pose significant clinical challenges due to their asymptomatic nature and potential to cause severe symptoms as they grow or invade surrounding organs. Treatment varies by tumor type, with surgery being crucial, especially for benign tumors and thymomas. The complex anatomy of the anterior mediastinum makes surgical approach selection critical for treatment outcomes.

Breast malignant phyllodes tumours are rare fibroepithelial neoplasms arising from periductal stromal cells, characterized by rapid progression and a high recurrence rate. The poor prognosis largely stems from the lack of effective therapeutic strategies, underscoring the insufficient understanding of their molecular mechanisms and therapeutic targets. Moreover, most previous studies have mainly focused on the tumour core, while the molecular features of the surrounding peritumoural tissue remain insufficiently explored.

This paper sought to determine whether uncoupling protein 2 (UCP2) regulates the immune phenotype of TAMs by modulating its own mitochondrial metabolic homeostasis in glioblastoma (GBM) cells, thereby influencing anti-tumor treatment response. This study evaluated UCP2 levels in clinical GBM samples and cell lines based on public databases, immunohistochemistry, RT-qPCR, and Western blot. A cell model with specific knockdown of UCP2 was constructed, and cell proliferation, migration and invasion, and apoptosis were detected. ATP measurement, Seahorse analysis, JC-1 staining, H2DCFDA, and MitoSOX staining were employed to assess mitochondrial metabolic function and ROS levels in GBM cells. A GBM-THP-1 co-culture system was established to evaluate the impact of UCP2 knockdown in GBM cells on macrophage polarization. A subcutaneous tumor model was established to evaluate the synergistic effect of UCP2 silencing + anti-PD-L1 therapy. UCP2 was upregulated in GBM tissues and accompanied by increased infiltration of M2-type TAMs. Specific knockdown of UCP2 in GBM cells inhibited cell proliferation and invasion, promoted apoptosis, and induced metabolic reprogramming by inhibiting mitochondrial energy metabolism, reducing mitochondrial membrane potential, and ROS accumulation. Co-culture with GBM cells with UCP2 knockdown promoted macrophage polarization toward the M1 type. UCP2 knockdown + anti-PD-L1 antibody inhibited GBM growth and increased the infiltration of M1-type TAMs. Knockdown of UCP2 in GBM cells reshapes the tumor microenvironment by regulating the tumor cell mitochondrial metabolism, thereby influencing their interaction with TAMs. This promotes M1-type repolarization and enhances the efficacy of anti-tumor treatment, making it a potential therapeutic target.

Distal cholangiocarcinoma (dCCA) is a malignant tumor characterized by a challenging diagnosis, high invasiveness, and extremely poor prognosis. Research on dCCA is limited by the scarcity of reliable patient-derived preclinical tumor models. This study established a novel human distal cholangiocarcinoma cell line, CBC3T-3, and systematically characterized its biological properties, genomic features, and potential for clinical application. This cell line was extracted from postoperative distal cholangiocarcinoma tumor from a 54-year-old male patient. It was stably passaged (> 50 generations) through primary culture and condition optimization, preserving the same pathology as that of the primary tumor. Whole-exome sequencing (WES) confirmed somatic mutations, tumor mutation burden, single-sample clonal structure, driver genes, and drug resistance genes in CBC3T-3 cells, revealing their genomic characteristics. Functional assays demonstrated that CBC3T-3 cells exhibit strong capabilities for proliferation, migration, and invasion in vitro. In a subcutaneous xenograft model in immunodeficient mice, palpable tumor nodules developed within 4 weeks, reflecting the clinical characteristics of rapidly progressive disease. Drug sensitivity analysis revealed that, compared with TFK-1 cells, CBC3T-3 cells presented significantly greater responses to paclitaxel, gemcitabine, and oxaliplatin but relatively poor responses to 5-FU and cisplatin. The integration of drug resistance gene findings from WES suggests that TP53 missense mutations may mediate primary resistance to cisplatin. The establishment of the CBC3T-3 cell line enhances the research toolkit for dCCA. Its genomic characteristics and functional plasticity provide a reliable preclinical tumor model for developing precision therapies and investigating drug resistance mechanisms.

Atypical and anaplastic (grade 2/3) meningiomas are associated with high recurrence rates and lack effective systemic therapies other than radiotherapy. Photodynamic therapy (PDT) using talaporfin sodium (TPS) generates selective cytotoxicity extending beyond resection margins and may improve local tumor control. Objective is to evaluate the feasibility, safety, and clinical outcomes of additional intraoperative PDT using TPS for grade 2/3 meningioma patients.

Chemotherapy lacks specificity, resulting in significant side effects on healthy tissues. Although molecularly targeted therapies have become standard treatments instead of chemotherapy, cancer heterogeneity hinders their effectiveness, and the availability of targeted antigens in clinical samples remains limited. Cell surface glycans have various "glycan patterns" composed of different glycan molecules, facilitating strong and selective cell-to-cell recognition. To better understand the factors influencing glycan pattern recognition in vivo, we created artificial glycoalbumins and identified cancer-specific accumulation patterns for various glycoalbumins modified with specific glycan patterns. To leverage the insights gained from these studies, we used glycoalbumin scaffolds as glycosylated therapeutic artificial metalloenzymes for cancer treatment by localizing their biological activity to avoid unwanted side effects. This review presents our foundational research that has driven artificial glycoalbumin-based targeting and subsequent adaptations for potential therapeutic applications.