Clinical T2N0 (cT2N0) esophageal squamous cell carcinoma (ESCC) represents a clinical grey zone between early-stage and locally advanced disease, and remains one of the most controversial scenarios in esophageal cancer management. The choice between upfront surgery and neoadjuvant therapy continues to vary across clinical guidelines and real-world practice. With the release of the 2026 International Society for Diseases of the Esophagus (ISDE) guidelines, this issue has once again drawn considerable attention. However, the existing controversy is not merely driven by differences in treatment strategies, but rather reflects the limited accuracy of pretreatment staging and the marked biological heterogeneity within the cT2N0 population. In this article, we review current evidence and international guidelines to analyze the underlying causes of these discrepancies, discuss the appropriate boundaries between upfront surgery and neoadjuvant therapy, and highlight future directions. We propose that the management paradigm for cT2N0 ESCC should shift from uniform treatment strategies toward precision risk stratification based on multidimensional clinical and biological information, thereby enabling more rational and individualized decision-making.

Oligometastatic disease (OMD) is considered an intermediate state between localized disease and widely metastatic disease, offering selected patients with metastatic esophageal cancer the possibility of long-term survival and even potential cure. In recent years, substantial progress has been made in oligometastatic esophageal cancer with advances in local treatment modalities, the widespread application of immunotherapy, and the development of precision medicine. In particular, randomized controlled evidence represented by the ESO-Shanghai 13 trial has, for the first time, demonstrated that local intervention combined with systemic therapy can provide significant survival benefits for patients with oligometastatic esophageal squamous cell carcinoma (ESCC), thereby promoting a shift in treatment strategy from purely palliative care to active multidisciplinary intervention. Meanwhile, the launch of the Oligometastatic Esophageal Squamous Cell Carcinoma (OMESQ) international consensus project marks the transition of oligometastatic ESCC research from borrowing experience from other tumor types toward disease-specific development. However, radiologically defined oligometastatic disease is not equivalent to biologically defined oligometastatic disease, and patient selection may be more important than the treatment modality itself. Based on recent advances in oligometastatic esophageal cancer, this commentary discusses the evolution of concepts, key clinical evidence, current controversies, and future directions. The author believes that research on oligometastatic esophageal cancer is moving from the exploratory stage of determining "whether local treatment is effective" toward a new stage of determining "how to precisely identify patients who are most likely to benefit." Establishing an ESCC-specific treatment framework based on tumor biological characteristics will become an important future direction in this field.

The incidence of early-onset colorectal cancer (EOCRC) has been rising globally in recent years, with an especially rapid increase in disease burden in China. Compared with late-onset colorectal cancer, EOCRC is more often diagnosed following symptomatic presentation, with greater diagnostic delay and more aggressive biological behavior. Patients are typically at critical life stages regarding career development and family building, and have urgent needs for fertility and sexual function preservation, and long-term quality of life. However, current domestic and international guidelines mostly target the general colorectal cancer population, and a systematic management framework tailored to the specific characteristics of early-onset patients is lacking. Therefore, the Hereditary Cancer Committee of the China Anti-Cancer Association organized a multidisciplinary expert panel-including specialists in colorectal surgery, medical oncology, radiation oncology, pathology, genetic medicine, reproductive medicine, psycho-oncology, and specialized nursing-to develop the Chinese Expert Consensus on the Diagnosis and Whole-Course Management of Early-Onset Colorectal Cancer (2026 version), based on evidence-based medicine and Chinese clinical practice. This consensus covers clinical issues such as the definition, epidemiological characteristics, screening and diagnosis, comprehensive treatment strategies, fertility and sexual function preservation, psychosocial support, and long-term follow-up of EOCRC, and presents 18 relevant recommendations. It aims to establish a multidisciplinary team-based whole-course management model that emphasizes both tumor control and long-term quality of life, providing a reference for the standardized diagnosis and treatment of EOCRC.

Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors characterized by remarkable clinical heterogeneity and genetic complexity. Conventional diagnostic and therapeutic strategies have largely relied on catecholamine assessment, anatomical imaging, and surgical resection; however, these approaches exhibit substantial limitations in metastatic risk stratification and personalized management for metastatic PPGL. Advances in genomics have enabled the establishment of the molecular cluster classification for PPGL, including pseudohypoxic, kinase-signaling, and Wnt-altered clusters, and corresponding strategies for precise nuclear medicine imaging and tumor surveillance. Recently, the refined application of nuclear medicine molecular imaging, the publication of international consensus guidelines on the management of patients with SDHB and SDHD mutations, and the approval of the hypoxia-inducible factor-2α (HIF-2α) inhibitor belzutifan, collectively have marked the entry of PPGL management into the era of precision medicine. Nonetheless, molecular cluster-guided targeted therapies for metastatic PPGL have not yet been incorporated into clinical guidelines, due to poorly characterized molecular mechanisms, a lack of patient-derived preclinical models, and the absence of cluster-specific, head-to-head clinical trials. Looking forward, the precision medicine in PPGL will move toward refined molecular subtyping, individualized treatment, integrated theranostic approaches, and multicenter collaboration.

Double-stranded linear DNA (dslDNA), considered to serve as a major precursor to integrated HBV DNA (iDNA), is generally located in the livers of patients with chronic HBV infection. Prior research has primarily focused on the role and mechanisms of HBV integration in the progression of hepatocellular carcinoma (HCC), demonstrating that iDNA can lead to genomic instability in the host and induce aberrant expression of host tumor-related genes around the integration sites, while viral proteins expressed by iDNA exhibit tumor-promoting effects. In recent years, the impact of iDNA-derived hepatitis B surface antigen on antiviral therapy in patients with chronic hepatitis B has received increasing attention with a deeper understanding of integrated HBV DNA. Consequently, the field has become a research hotspot and challenge in determining how to eliminate or silence iDNA to improve functional cure in patients with chronic hepatitis B. This paper aims to provide new sights to the clinical significance of iDNA and a theoretical basis for optimizing antiviral therapy strategies by summarizing the occurrence mechanisms of iDNA and its impact on the onset and progression of hepatocellular carcinoma and antiviral therapy for patients with chronic hepatitis B.

Human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV + OPSCC) generally has favorable outcomes yet remains prone to late recurrence. Durable control likely depends on persistent tumor-specific CD8+ T cells, but their persistence and function in metastasis are poorly understood.

We integrated bulk RNA sequencing (n = 56) with single-cell RNA and paired T-cell receptor (TCR) sequencing of tumor-infiltrating CD8+ T cells (n = 4), including a longitudinal primary-lung metastasis pair obtained three years after curative therapy. HPV genotyping, HLA typing, epitope prediction, and NFAT-reporter Jurkat-luciferase assays were used to identify and functionally validate HPV16 E6/E7-specific TCRs. Repertoire tracking and single-cell/bulk transcriptomics were evaluated.

HPV + tumors showed higher inferred CD8+ T cell infiltration and more favorable prognosis than HPV- tumors. Single-cell analysis revealed oligoclonally expanded exhausted clusters enriched in HPV tumor-specific CD8+ T cells. We isolated and functionally validated nine patient-derived HPV16 E6/E7-specific TCRs. High-avidity receptors recognizing an alternatively spliced region in E6 (aa 49-110; E6*) persisted in metastatic lesions, whereas lower-avidity clones, including an E7_11-19-specific TCR currently under clinical investigation, were lost. Compared with the primary tumor, metastatic lesions showed reduced stem-like/TCF7-associated CD8+ T-cell populations and enrichment of HPV-specific CD8+ T cells expressing KLRB1 and ZNF683, consistent with a tissue-adapted TRM-like transcriptional state with inhibitory signaling features.

High-avidity, KLRB1 + HPV-specific CD8+ T cells represent a persistent effector subset with prognostic and therapeutic relevance to HPV + OPSCC. Their persistence in metastatic lesions and association with reduced recurrence risk support further investigation of KLRB1-associated HPV-reactive T-cell states as biomarkers and immunotherapeutic targets.

Bladder cancer (BC) is considered one of the most prevalent malignant cancers of the urinary system. Recently, autophagy was found to be involved in tumor development.

Investigating the link between BC and autophagy, highlighting the role of ER stress in tumor growth and invasiveness.

Sixty urothelial carcinoma patients recruited to this study were divided into 2 groups: Low-grade BC (LGBC) and High-grade BC (HGBC), which were further classified as muscle-invasive (HGMI) or non-muscle-invasive (HGNMI). Control tissue samples were collected from the safety margin. Levels of ATG5 and caspase 3 were determined using qRT-PCR; CHOP levels by ELISA; and malondialdehyde using the lipid peroxide assay kit. LC3A expression was detected by immunohistochemistry.

Significant upregulation of tissue levels of ATG5, CHOP, MDA and LC3A was observed in tumor tissue samples from all groups compared to control, and in MIBC compared to NMIBC, with significant relations between their levels and LN involvement. Caspase-3 was significantly downregulated in HGBC compared to LGBC. Levels of ATG5, CHOP and LC3A can discriminate between normal and malignant urothelial tissue and between invasive and non-invasive bladder cancer.

Expression of tissue autophagy biomarkers is associated with aggressive clinicopathological features (muscle invasion) in bladder cancer.

Prostate cancer (PCa) is among the highest incidence malignancies in men, with high rates of inevitable resistance development, relapse, and mortality. Castration-resistant prostate cancer (CRPC) continued to pose substantial therapeutic challenges, highlighting the urgent need for effective treatment options. This study assessed the marine cembranoid sarcophine activity against the progression and recurrence of the metastatic CRPC (mCRPC) in mouse xenograft models. Protein and phosphorylation levels were assessed by immunoblotting and mRNA expression by qPCR and RNA sequencing. The in vivo efficacy was evaluated through tumor progression over 3 weeks followed by primary tumor excision and recurrence monitoring over an 8-week course. Sarcophine significantly reduced the mCRPC CWR-R1ca tumor volume by 74.1% and suppressed the epigenetic regulators EZH2 and SMYD2; lineage plasticity factors ASCL1 and BRN2; Wnt/stemness signaling markers β-catenin and LGR6; AKT total expression and activation; and invasion-associated proteins TRPC4 and MMP2 in primary tumors. Sarcophine effectively prevented the mCRPC locoregional recurrence, as well as lung and spleen distant recurrences, and effectively reduced recurrence in other organs. Transcriptomics-RNA-Seq analysis of primary tumors identified 2697 downregulated and 3534 upregulated genes, indicating broad transcriptional reprogramming following sarcophine treatments. These findings demonstrate coordinated suppression of multi-oncogenic pathways and validate the therapeutic potential of sarcophine to control mCRPC.

Hepatitis B virus (HBV) infection remains a major global health burden, with chronic infection leading to severe liver diseases including cirrhosis and hepatocellular carcinoma (HCC). HBV-encoded X protein (HBx) plays a critical role in viral replication and pathogenesis by modulating host cellular processes, including autophagy and lysosomal function. However, the molecular mechanisms by which HBx disrupts lysosomal biogenesis and autophagic degradation remain elusive. In this study, we show that HBx downregulates the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, which leading to impaired lysosomal acidification and autophagosome-lysosome fusion. Mechanistically, HBx-mediated TFEB downregulation involves the CUL4A (Cullin 4A)/CUL4B (Cullin 4B)-DDB1 (DNA damage-binding protein 1) E3 ubiquitin ligase complex and is dependent on the DDB1-interacting motif in HBx. HBx mutants defective in DDB1 binding (HBx^R96E and HBx^ΔDBD) fail to downregulate TFEB or impair lysosomal function. Collectively, our findings identify a pathway by which HBx disrupts lysosomal function via CUL4A/CUL4B-DDB1-dependent TFEB downregulation, providing insights into HBV-associated liver pathogenesis and highlighting potential targets for therapeutic intervention.

Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by rapid progression, therapeutic resistance, and poor patient prognosis. Emerging evidence highlights the critical role of long non-coding RNAs (lncRNAs) in GBM pathogenesis, particularly through their interactions with RNA-binding proteins (RBPs). These interactions form complex regulatory networks that influence multiple GBM hallmarks, such as sustained proliferation, induction of angiogenesis, and immune evasion. Additionally, these interactions play a pivotal role in maintaining glioma stem-like cells, a subpopulation responsible for tumor recurrence and resistance to conventional therapies. Understanding the mechanistic basis of lncRNA-RBP interactions offers promising opportunities for therapeutic intervention. Targeting these networks could enable the development of novel and more effective treatment strategies. This review provides an in-depth analysis of the molecular mechanisms by which lncRNA-RBP complexes promote GBM development.