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.

Although cancer immunotherapy has been flourishing, the number of targets for Food and Drug Administration (FDA)-approved cancer immunotherapeutics has remained small and mostly limited to proteins. The approval of dinutuximab, an anti-GD2 for treating high-risk neuroblastoma in 2015, marks the first new agent targeting glycosphingolipids (GSLs). Recently, our research group demonstrated that another GSL, Globo H ceramide (GHCer), which was previously reported to be the most prevalent cancer-associated antigen in many epithelial cancers, is an independent poor prognostic factor for breast cancer, hepatoma, cholangiocarcinoma, and gallbladder cancer. We had further shown that GHCer is shed from tumor cells to extracellular vesicles (EVs), which are then incorporated into endothelial cells in the tumor microenvironment to promote angiogenesis. Molecular dynamics simulation and other studies also revealed fucose-dependent changes in the glycan conformation of GHCer conducive for a complex formation between translin-associated factor X (TRAX) protein and GHCer, thus highlighting the molecular mechanism of how GHCer facilitated dissociation of phospholipase C beta 1 (PLCβ1) from TRAX, thereby enhancing angiogenesis. Thus, GHCer is not only a tumor antigen associated with adverse prognostic impact but also acts as an immune checkpoint and an angiogenic factor to shape the tumor microenvironment. These findings provide strong rationales for developing Globo H-targeted immunotherapy.

Resistance to 5-fluorouracil (5-FU) remains a major challenge in the treatment of colorectal cancer (CRC). Here, we identify ETS variant transcription factor 7 (ETV7) as significantly upregulated in CRC tissues and cell lines, with elevated expression associated with poor clinical prognosis. Functional assays demonstrate that ETV7 enhances CRC cell proliferation, invasion, and resistance to 5-FU. Mechanistically, ETV7 transcriptionally upregulates CXCL1, leading to increased neutrophil recruitment and enhanced formation of neutrophil extracellular traps (NETs). The resulting NETs-enriched tumor microenvironment promotes tumor aggressiveness and chemoresistance. Pharmacological inhibition of CXCL1 or degradation of NETs effectively attenuates ETV7-driven malignant phenotypes in vitro and in vivo. Collectively, these findings establish an ETV7-CXCL1-NETs axis that contributes to 5-FU resistance in CRC and suggest that targeting this pathway may improve chemotherapy response.

Metabolic reprogramming is a hallmark of cancer, with the Warburg effect-driven aerobic glycolysis leading to a substantial accumulation of lactate in the tumor microenvironment. For a long time, lactate was considered a mere metabolic end product; however, recent studies have found that it acts as an important signaling molecule, profoundly influencing tumor progression by inducing a novel post-translational modification - lactylation. Lactylation, driven by lactate, occurs on both histones and non-histone proteins and is finely regulated by the 'writer' 'eraser' and 'reader' mechanisms, thereby altering the function of target proteins and gene expression. This review systematically explores the bidirectional regulatory network between glycolytic reprogramming and lactylation: on one hand, key glycolytic regulators promote lactate production, thereby increasing lactylation levels; on the other hand, lactylation can feedback to regulate the activity and expression of key glycolytic enzymes, forming a pro-tumor positive feedback loop. This interaction plays a central role in tumor proliferation, metastasis, DNA damage repair, and immune evasion. Consequently, targeting lactate production, lactate transport, or the lactylation process itself has emerged as a highly promising anti-cancer strategy and shows potential synergy with existing therapies such as immune checkpoint inhibitors. In-depth analysis of the glycolysis-lactylation axis will provide a crucial theoretical basis for developing novel cancer treatment approaches.
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Global cancer statistics in 2022 ranked lung cancer as the leading cause of cancer incidence and mortality worldwide, with lymph node metastasis serving as a pivotal determinant of prognosis and treatment strategy. Extranodal extension (ENE) refers to the pathological phenomenon where tumor cells breach the lymph node capsule and invade surrounding tissues. In non-small cell lung cancer (NSCLC), although ENE has not yet been formally incorporated into the tumor-node-metastasis (TNM) staging system, its clinical value is gaining increasing attention. This review systematically summarizes the current research progress regarding the definition, diagnostic approaches, prognostic significance, and treatment implications of ENE in NSCLC, analyzes existing challenges, and proposes future directions. The goal of this paper is to provide insights for optimizing clinical practice and guiding subsequent research.
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First-line immunotherapy for advanced non-small cell lung cancer (NSCLC) shows significant survival benefits in patients without driver mutations, but the optimal duration of treatment remains controversial. Some studies support limiting immunotherapy to 2 years, arguing that longer treatment does not bring additional survival benefits; while other studies believe that treatment should continue until disease progression to maximize survival benefits. This article systematically reviews the current research progress on the duration of immunotherapy and discusses the potential predictive value of biomarkers such as circulating tumor DNA (ctDNA), the best efficacy response, and programmed cell death ligand 1 (PD-L1) expression levels in individualized treatment decisions. More prospective studies, especially biomarker-driven trials, are still needed to clarify the optimal duration of treatment and establish an individualized treatment strategy based on multidimensional indicators.
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Serous effusion is a common complication in patients with advanced lung cancer, which often indicates that the tumor has metastasized to the pleura or other serosal membranes. It is essential to achieve an accurate diagnosis and pathological classification of tumor cells in effusion to guide clinical treatment. However, there are limitations to relying solely on morphological diagnosis, especially in atypical cases where diagnostic uncertainty is common. The International System for Serous Fluid Cytopathology (TIS) proposes a standardized hierarchical diagnostic framework that integrates morphology and auxiliary techniques. Nevertheless, its clinical application value in the Chinese lung cancer population remains insufficiently validated. This study aimed to systematically evaluate the diagnostic performance of the TIS system in the assessment and classification of serous effusions based on a large sample of lung cancer cases.

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths worldwide, and its occurrence and development are closely related to complex molecular mechanisms. Alternative splicing of precursor mRNA is a key step in gene expression regulation, and its dysregulation is common in tumors. The serine/arginine-rich splicing factor (SRSF) family, a core protein family in splicing regulation, has been confirmed to play oncogenic roles in various cancers. However, systematic research on the SRSF family in NSCLC remains insufficient. This study aims to systematically analyze the specific expression patterns, clinical prognostic value, collaborative mechanisms and potential biological functions of SRSF individual members in NSCLC by the combination of bioinformatics analysis and experimental verification.

The prognosis for non-small cell lung cancer (NSCLC) with leptomeningeal metastasis (LM) is extremely poor. However, in oncogene addicted patients, the emergence of targeted therapies with high central nervous system (CNS) penetration is significantly reshaping the treatment landscape. Existing guidelines, which often favor conservative strategies, are no longer sufficient to meet the demands of precision medicine. To address this challenge, the Metastasis Lung Cancer Collaboration Group, Youth Specialists Committee of Beijing Medical Reward Foundation convened multidisciplinary experts from Medical Oncology, Radiology, Pathology, Radiotherapy, and Neurosurgery. Based on evidence-based medicine from the past decade and clinical practice experience, they have developed the Chinese expert consensus on clinical management of oncogene addicted NSCLC with leptomeningeal metastasis (2026 edition). This consensus emphasizes that the diagnosis of LM should be based on a comprehensive assessment of clinical symptoms, magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) cytology. It also highlights the critical role of CSF molecular liquid biopsy in clarifying driver gene status and assessing treatment efficacy. In terms of treatment, this consensus advocates for a fundamental paradigm shift: therapy should be led by a multidisciplinary team (MDT), with high-CNS-penetration targeted therapies as the first-line intervention, while local treatments (such as intrathecal injection and radiotherapy) are positioned as supplementary measures. The consensus provides a series of expert recommendations on key aspects, including the selection of high-CNS-penetration tyrosine kinase inhibitors (TKIs), the application of intrathecal chemotherapy, the timing of radiotherapy, and palliative surgery. It aims to establish proactive, individualized treatment standards for patients with NSCLC LM in China, based on molecular subtyping and MDT collaboration, thereby improving patient survival outcomes.
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Tumor mutational burden (TMB) and PD-L1 are established biomarkers for guiding immune checkpoint inhibitor (ICI) therapy in advanced non-small cell lung cancer (NSCLC). As ICI use expands into early-stage disease, we explored the feasibility of using TMB, which can be determined via a comprehensive genomic profiling assay along with EGFR and ALK genomic alterations, as a biomarker for outcomes in both neoadjuvant and adjuvant settings. TMB-high status (≥10 mut/Mb) showed a numerically higher, but not statistically significant, rate of pathological complete response among patients receiving neoadjuvant ICI and significantly associated with more favorable time to recurrence in patients receiving adjuvant ICI, particularly among patients with PD-L1 expression <50%. TMB should be considered in future early-stage NSCLC ICI clinical trials to further validate these results.

Proton beam therapy (PBT) has proven to be highly effective in treating pediatric medulloblastoma, offering both excellent therapeutic outcomes and reduced side effects. However, factors influencing tumor response following PBT remain poorly defined, including the optimal interval time between surgery and PBT initiation (ISP).