TFE3 translocation renal cell carcinoma (tRCC), an aggressive kidney cancer driven by TFE3 gene fusions, is frequently misdiagnosed owing to morphologic overlap with other kidney cancer subtypes. Conventional liquid biopsy assays that detect tumor DNA via somatic mutations or copy number alterations are unsuitable for tRCC since it often lacks recurrent genetic alterations and because fusion breakpoints are highly variable between patients. We reasoned that epigenomic profiling could more effectively detect tRCC because the driver fusion constitutes an oncogenic transcription factor that alters gene regulation. By defining a TFE3-driven epigenomic signature in tRCC cell lines and detecting it in patient plasma using ChIP-seq, we distinguished tRCC from clear-cell RCC (AUC = 0.86) and samples of individuals without evidence of cancer (AUC = 0.92) at low tumor fractions (<1%). This work establishes a framework for noninvasive epigenomic detection, diagnosis, and monitoring of tRCC, with implications for other mutationally quiet, fusion-driven cancers.

Metastatic hormone-sensitive prostate cancer (mHSPC) is a clinically and molecularly heterogeneous disease. Recent insights into the biology underlying disease presentation, volume of disease, and response to therapies are starting to point toward biomarkers to improve selection for intensified and deintensified treatment strategies. In addition, the therapeutic landscape is rapidly changing, with new biomarker-driven studies targeting genotype (e.g., BRCA or PTEN mutant) and phenotype (e.g., prostate-specific membrane antigen status) in development for mHSPC. A better understanding of tumor heterogeneity, clonal evolution, and metastatic homing in prostate cancer will hopefully inform future strategies for local and systemic disease control, personalized monitoring strategies, and improved patient outcomes.

Circadian clocks govern daily rhythms in cellular and physiological processes, including cell cycle, DNA repair, metabolism, and immune function, that influence cancer development and treatment response. Disruption of circadian regulators either promotes or suppresses malignancy depending on tumor type and biological context. This duality likely reflects systemic rewiring of circadian physiology and direct interactions between clock components and oncogenic pathways. These insights hold clinical relevance for the field of chronotherapy, which seeks to enhance therapeutic efficacy and minimize toxicity by aligning drug administration with circadian rhythms or by targeting elements of the molecular clock. In this Review, we highlight the promise of integrating circadian biology into precision oncology and underscore the importance of cancer type-specific investigations to harness the full therapeutic potential of chronotherapy in cancer.

About 10% to 15% of patients with ischemic stroke have a history of cancer, half of whom have active malignancy at the time of stroke. With improved cancer treatments extending patient survival, the coprevalence of these diseases has increased steadily since 2000. This has sparked considerable growth in research and knowledge on this topic. Approximately half of ischemic strokes in patients with active cancer are due to conventional mechanisms, although cancer-related factors may contribute. The remaining half of ischemic strokes in this population are typically classified as cryptogenic or attributed to cancer-specific mechanisms. These cryptogenic strokes often have characteristic risk markers and clinical features and are extremely high risk for recurrent stroke and other adverse events, distinguishing them from other stroke subgroups. Recent epidemiological, translational, and histopathological data indicate that many of these events are likely caused by the cancer itself through multifactorial prothrombotic processes. In this scientific statement incorporating multidisciplinary expertise, we critically appraise and synthesize recent evidence and provide clinical suggestions on the epidemiology, presentation, evaluation, pathophysiology, and treatments for ischemic stroke in patients with active cancer. In addition, we propose a novel classification for ischemic stroke attributed to cancer itself, which we define as cancer-related stroke to enable consistent nomenclature and to harmonize stroke classification across clinical practice and research. This system is based on routinely available clinical data and includes different categories for certainty of causality, relating to the patient's distinctive clinical features and estimated risk for recurrent thromboembolism. We hope this framework spurs dedicated controlled trials to address areas of clinical uncertainty.

Pseudomyogenic Hemangioendothelioma (PMHE), also known as epithelioid sarcoma-like hemangioendothelioma, is a rare, indolent, low-grade vascular tumor. It typically presents as firm cutaneous nodules, with a predilection for the lower extremities and a male predominance. While numerous cases have been reported in pathology literature, detailed radiologic descriptions, particularly of soft tissue origins, are scarce. This report aims to bridge this gap by presenting a rare case of PMHE with comprehensive imaging findings.

We report on a 67-year-old male who presented with painful, palpable papules on his right buttock. MRI revealed multifocal dermal nodules demonstrating low signal intensity on T1-weighted images and high signal intensity with a distinctive peripheral high-signal halo on T2-weighted images. Notably, T1 gadolinium fat-saturated sequences exhibited marked enhancement with a characteristic peripheral rim enhancement pattern. The lesions were confined to the cutaneous layer. Initial radiological differentials included post-inflammatory granuloma and sarcoma. Histopathological examination confirmed PMHE. PET/CT demonstrated no evidence of systemic metastasis, and the patient has remained recurrence-free for two years following surgery.

This report highlights a rare case of cutaneous PMHE and details its distinctive MRI features, particularly the peripheral rim enhancement. Given its rarity and often non-specific clinical and imaging presentations, there is a significant potential for misdiagnosis. Therefore, it is crucial for radiologists to be aware of PMHE and familiarize themselves with its characteristic radiological patterns to facilitate accurate, timely diagnosis and ensure appropriate patient management.

&lt;b&gt;Background and Objective:&lt;/b&gt; Oral Squamous Cell Carcinoma (OSCC), particularly tongue malignancies, remains a major global health concern due to late diagnosis and limited treatment options. &lt;i&gt;Salvadora persica&lt;/i&gt; (Miswak), traditionally used by ancient Arabs for oral hygiene, contains numerous bioactive compounds with potential therapeutic value. This study aimed to evaluate the antioxidant properties of Miswak extract using different solvents, quantify its total phenolic and flavonoid content and assess its anticancer activity against an oral cancer cell line through &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in silico &lt;/i&gt;approaches. &lt;b&gt;Materials and Methods:&lt;/b&gt; Miswak extracts were prepared using water, acetone and ethanol to compare antioxidant capacity and phytochemical content. The extract exhibiting the highest activity was selected for further analysis. The ethanolic extract was subsequently tested on the human tongue carcinoma cell line (HNO97) using the Sulforhodamine B (SRB) assay to determine cytotoxicity. The ELISA was conducted to quantify TNF-α and VEGF-A levels, while real-time PCR was used to measure the expression of caspase-3 and caspase-7. Molecular docking was performed to evaluate the binding affinity of Miswak-derived compounds toward DAPK1, a key protein involved in regulating apoptosis. Statistical analyses were applied to assess the significance of the findings. &lt;b&gt;Results:&lt;/b&gt; The ethanolic extract exhibited the highest antioxidant activity and was selected for anticancer evaluation. SRB assay results showed potent cytotoxicity against HNO97 cells with an IC&lt;sub&gt;50&lt;/sub&gt; of 260.03 μg/mL. The ELISA confirmed significant downregulation of TNF-α and VEGF-A, indicating pronounced anti-inflammatory and anti-angiogenic effects. Real-time PCR demonstrated upregulation of caspase-3 and caspase-7, suggesting activation of apoptotic pathways. Molecular docking supported these observations by revealing strong binding affinities of the extract's bioactive compounds to DAPK1. &lt;b&gt;Conclusion:&lt;/b&gt; The ethanolic extract of &lt;i&gt;Salvadora persica&lt;/i&gt; demonstrates promising antioxidant, anti-inflammatory, anti-angiogenic and pro-apoptotic properties, indicating its potential as a natural therapeutic candidate for oral squamous cell carcinoma. These findings provide a strong foundation for further &lt;i&gt;in vivo&lt;/i&gt; and preclinical studies to validate its efficacy and safety.

Acute myeloid leukaemia (AML) is a highly heterogeneous haematologic malignancy. Current therapeutic strategies include chemotherapy, targeted therapy and haematopoietic cell transplantation (allo-HSCT) and autologous haematopoietic cell transplantation (auto-HSCT). The graft-versus-leukaemia (GVL) effect and graft-versus-host disease (GVHD) in allo-HSCT remain major research foci, with emerging evidence highlighting the synergistic roles of T cells and natural killer (NK) cells in allo-HSCT immunity. This review systematically integrates the cooperative immunological interactions between T cells and NK cells and elucidates their critical significance in post-transplant immunotherapy.

This review systematically summarizes the cytotoxic mechanisms, immune reconstitution processes and related immunotherapeutic approaches involving T cells and NK cells in AML in the context of allo-HSCT and further elucidates their unique role in post-transplant immune regulation from the perspective of coordinated T-cell and NK-cell interactions.

T cells and NK cells exert synergistic effects in post-transplant immune reconstitution, GVL responses, GVHD regulation and subsequent immunotherapeutic interventions. Early NK-cell reconstitution provides a critical window for the restoration of T-cell function, whereas cytokines derived from T cells, such as IL-2 and IL-15, further enhance NK-cell activity. This dynamic immunological interplay not only shapes the balance between GVL and GVHD, but also informs the development of post-transplant immunotherapeutic strategies.

The dynamic interplay between T cells and NK cells plays a pivotal role in allo-HSCT for AML. This review systematically integrates the cooperative functions of T cells and NK cells within the allo-HSCT immune landscape, offering new perspectives for advancing post-transplant immunotherapy. A deeper understanding of these mechanisms is expected to provide a theoretical foundation for optimizing post-transplant immune interventions in AML patients and for developing more precise therapeutic strategies.

Pulmonary enteric adenocarcinoma (PEAC) is a distinct subtype of non-small cell lung cancer (NSCLC) whose histomorphology and immunophenotype closely resemble those of metastatic colorectal adenocarcinoma; its pathogenesis and standard treatment strategies have yet to be clearly established. Here, we reported a case of PEAC harboring epidermal growth factor receptor (EGFR) exon 19 deletion mutation with high programmed cell death ligand 1 (PD-L1) expression. The patient showed no meaningful response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs), including the first-generation (Icotinib), the second-generation (Afatinib) and the third-generation (Aumolertinib). Trophoblast cell surface antigen 2-antibody-drug conjugate (TROP2-ADC) and immune checkpoint inhibitors (ICIs) combined with Bevacizumab also resulted in limited efficacy. Based on the clinical features and treatment response of this case, we reviewed the published literature about the pathological characteristics, mutational landscape, and current therapeutic approaches for PEAC, with a particular focus on the therapeutic challenges and future research directions for EGFR-mutant PEAC, aiming to provide insights for clinical practice and further studies.
.

Stage III non-small cell lung cancer (NSCLC) accounts for approximately 30% of newly diagnosed NSCLC cases, and the vast majority of these patients present with unresectable disease. Its unresectable nature makes definitive chemoradiotherapy the cornerstone of treatment. In recent years, with immune checkpoint inhibitors (ICIs) becoming a major research focus in lung cancer, increasing evidence demonstrates that the combination of radiotherapy and immunotherapy (iRT) can significantly enhance antitumor efficacy through synergistic mechanisms. The groundbreaking results of the landmark PACIFIC trial further established consolidation immunotherapy following concurrent chemoradiotherapy as the standard of care. However, controversies persist regarding optimal radiotherapy strategies, timing of immune intervention, management of adverse reactions, and exploration of biomarkers. This review aims to systematically elucidate the synergistic mechanisms of iRT, summarize clinical trial advances under different iRT treatment modalities (concurrent, consolidation and induction), and provide an in-depth analysis of key issues in current clinical practice along with future research directions.
.

Lung cancer, one of the leading causes of cancer-related deaths worldwide, severely influences patients' quality of life and prognosis due to its complication of brain metastasis (primarily involving the brain parenchyma). While traditional treatments such as surgery, radiotherapy, and chemotherapy have demonstrated efficacy in clinical practice, their application remains limited due to toxicity and patient tolerance issues. Emerging targeted therapies and immunotherapies, which exhibit significant efficacy with fewer side effects, still face challenges including partial drug resistance and genetic mutations. In recent years, research on the association between gut microbiota and lung cancer brain metastasis has gained prominence. Its mechanism of action may influence the progression of brain metastasis through multidimensional interactions via the brain-gut axis, involving neuroendocrine and immune pathways. This review examines specific mechanisms by which gut microbiota modulate lung cancer brain metastasis through immune regulation, endocrine-metabolic regulation, and neurotransmitter control via the brain-gut axis, as well as therapeutic and traditional medicine research on regulating gut microbiota in lung cancer brain metastasis. It aims to provide theoretical support and identify potential clinical therapeutic targets for the prevention and treatment of lung cancer brain metastasis.
.