Renal cell carcinoma (RCC) is a biologically heterogeneous malignancy characterized by variable clinical behavior and diverse molecular phenotypes. Although immune checkpoint inhibitors and targeted therapies have transformed the treatment landscape of advanced RCC, clinically validated biomarkers capable of improving risk stratification, therapeutic-decision making and disease monitoring remain lacking. Kidney injury molecule-1 (KIM-1), also known as hepatitis A virus cellular receptor-1 (HAVCR1) or T-cell immunoglobulin and mucin domain-containing protein-1 (TIM-1), has emerged as a biologically compelling investigational biomarker e because of its close relationship to proximal tubular epithelial injury and renal carcinogenesis. KIM-1 is a transmembrane glycoprotein minimally expressed in normal kidney tissue but markedly upregulated in dedifferentiated proximal tubular epithelial cells following injury, and in clear cell RCC, where its extracellular domain can be shed into plasma and urine. Beyond its role as a marker of tubular injury, KIM-1 participates in immune regulation, phagocytosis, inflammatory signaling and tissue remodeling, supporting its potential relevance to tumor biology. Clinical studies have demonstrated associations between elevated circulating KIM-1 levels and RCC diagnosis, recurrence risk, and survival outcomes, particularly in localized and postoperative disease settings. KIM-1 has additionally been investigated as a therapeutic target through antibody-drug conjugate approaches. Despite promising translational data, important limitations yet remain. Current evidence is predominantly prognostic rather than predictive, and substantial analytical and biological challenges continue to limit implementation. Assay standardization, clinically meaningful cutoffs, specimen selection, timing of sampling, and confounding by chronic kidney disease or nonmalignant renal injury remain incompletely resolved. Furthermore, evidence supporting incremental value beyond established clinicopathologic models remains limited. This review critically evaluates the biological rationale, analytical considerations and clinical evidence supporting KIM-1 in RCC. Particular emphasis is placed on distinguishing prognostic, predictive, pharmacodynamic, and therapeutic applications, as well as defining the evidentiary gaps that must be addressed before clinical implementation. Current evidence is derived predominantly from retrospective and exploratory analyses, and important limitations remain regarding assay standardization, biological specificity, chronic kidney disease-related confounding, and prospective validation. The review concludes with a summary of the evolving landscape of KIM-1-directed biomarker strategies in RCC, which may ultimately contribute to improved biologic risk stratification and biomarker-driven clinical investigation in RCC.

Aim: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm with few reported mandibular cases. This review aims to describe the clinical characteristics, surgical management and outcomes of 13 mandibular IMT cases, and to introduce the Jaw in a Day (JIAD) approach as a novel surgical option. Methods: PubMed, Web of Science and Embase were searched systematically. From an initial pool of 261 articles, 13 studies met the inclusion criteria and were reviewed. Results: Thirteen mandibular IMT cases were identified in the literature. A new case is also presented: a 15-year-old female treated with surgical excision using the JIAD approach. At 12-month follow-up, oral function was restored with no disease recurrence. Discussion: Mandibular IMT is exceedingly rare. The JIAD approach offers immediate reconstruction with satisfactory functional outcomes, as supported by both the current case and the reviewed literature. Conclusions: The JIAD surgical approach may represent an effective management strategy for mandibular IMT. Further cases are needed to validate this approach and establish standardized treatment protocols.

Hepatocellular carcinoma (HCC) imposes a substantial health burden in China. Finotonlimab plus bevacizumab recently prolonged progression-free survival (PFS) and overall survival (OS) vs. sorafenib, but its economic value remains unknown. Here we evaluated the cost-effectiveness of finotonlimab plus bevacizumab vs. sorafenib from the Chinese healthcare system perspective. Parametric survival models were fitted to extrapolate PFS and OS. Total costs, life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), incremental net monetary benefit (INMB), and incremental net health benefit (INHB) were estimated at a willingness-to-pay (WTP) threshold of $27,906 per QALY. Uncertainty was evaluated by one-way and two-way sensitivity analyses, probabilistic sensitivity analysis (PSA), subgroup analyses, scenario analyses, and price simulations. In the base-case analysis, sorafenib yielded 1.74 LYs and 1.25 QALYs at a total cost of $10,303.10, whereas finotonlimab plus bevacizumab yielded 3.01 LYs and 2.18 QALYs at a total cost of $58,595.49. Compared with sorafenib, the combination increased costs by $48,292.39 and generated gains of 1.27 LYs and 0.93 QALYs, resulting in ICERs of $38,203.46 per LY and $51,899.31 per QALY. INMB (-$22,325.82) and INHB (-0.80 QALYs) were negative. Sensitivity analyses identified PFS utility and bevacizumab cost as key drivers, but all ICERs remained above the WTP threshold. In PSA, the mean ICER was $50561.81 per QALY, and the probability of cost-effectiveness was 0% at the prespecified threshold. Based on the assumptions and inputs used in the present model, finotonlimab plus bevacizumab was unlikely to be cost-effective compared with sorafenib at the prespecified WTP in China.

The therapeutic management of intermediate-risk differentiated thyroid carcinoma (DTC) remains a clinical conundrum, often caught between the Scylla of over-treatment and the Charybdis of disease persistence. While conventional risk stratification models predominantly emphasize histopathological and tumour-specific characteristics, the study by Piticchio et al. offers a salient contribution by shifting the focus towards the host's systemic immune landscape. By identifying the pre-radioiodine, RAI, Monocyte-to-Lymphocyte Ratio (MLR) as a robust, independent predictor of early recurrence, the authors provide a potentially transformative biomarker that enhances prognostic granularity beyond traditional staging. However, the interpretation of these haematological indices necessitates a nuanced understanding of the physiological milieu at the time of sampling. Specifically, the influence of profound iatrogenic hypothyroidism, induced by levothyroxine withdrawal, poses a significant confounding variable that may modulate circulating leucocyte dynamics independently of tumour biology. Furthermore, while the lack of prognostic utility for nutritional indices like the PNI and NRI underscores the preserved metabolic status of this cohort, it also invites a reassessment of whether more sensitive markers of body composition are required. This abstract evaluates the clinical implications of utilizing inflammatory ratios to refine postoperative surveillance and argues for the integration of host-immune interfaces into future oncological frameworks. Ultimately, while the MLR demonstrates significant potential for personalizing follow-up, prospective validation across diverse ethnic cohorts and under varying thyroid-stimulating hormone stimulation protocols is essential to establish its universal clinical utility.

Pseudomyxoma peritonei (PMP) is characterized by progressive mucus accumulation, extensive stromal fibrosis, rare extraperitoneal metastasis, limited therapeutic options, and frequent recurrence. However, the microenvironmental ecosystem of PMP, particularly in metastatic lesions, remains poorly understood. Here, we integrated single-cell RNA sequencing, whole-exome sequencing, bulk RNA sequencing, and histopathologic validation to construct a high-resolution atlas of primary and paired metastatic tumors. Epithelial cells showed distinct functional states, including a TFF3⁺ mucus secretion-associated state and a MACC1⁺ malignant-associated state. Metastatic lesions showed coordinated microenvironmental reprogramming, including POSTN⁺ fibrosis-associated fibroblasts, CXCL5⁺ macrophages linked to local immunosuppressive signaling, and immune exclusion associated with a collagen-rich stromal barrier. We also observed extensive lipid metabolic activity and identified a candidate pro-angiogenic network involving POSTN⁺ fibroblasts, RSPO3⁺ pericytes, and endothelial cells, potentially mediated by VEGFA-VEGFR2 signaling. Retrospective observations from three recurrent PMP cases further suggested the potential therapeutic value of VEGFR2-targeted anti-angiogenic therapy. Overall, this study provides a comprehensive single-cell transcriptomic atlas of PMP and a resource for developing novel and combination therapeutic strategies.

Bronchiolar adenoma (BA) is a generally benign peripheral lung neoplasm with a bilayered structure of basal and luminal cells. Recently, an increasing number of bronchiolar adenoma-like tumor with squamous epithelial metaplasia (BATSM) have been reported, raising the question of whether they represent variant subtypes of BA or potentially novel tumor entities. Pulmonary metastasis of ameloblastoma (MA) shares morphological similarities with BATSM, exhibiting TTF-1/Napsin A-positive luminal cells and P40/P63-positive basal cells; this overlap can lead to misdiagnosis of MA as BATSM. We collected 5 MA and 10 BATSM cases, analyzing their morphology, immunohistochemistry, elastic fiber staining and molecular pathology. MA presents as well-circumscribed bronchiole-unrelated nodules with alveolar destruction, intraluminal serous secretions, and Calretinin-positive stellate reticulum-like cells. BATSM is bronchiole-associated, preserves alveolar architecture, and is Calretinin-negative with weak basal TTF-1 positivity. 80% of MA cases harbored BRAF V600E mutations; 30% of BATSM cases exhibited EGFR exon 20 insertions. This study highlights the need for integrating clinical history, morphology, immunohistochemistry and molecular testing to avoid misdiagnosing MA as BATSM.

Ibrutinib has demonstrated inhibition of ErbB/HER tyrosine kinases in preclinical models. This Phase I/II study investigated the safety, efficacy, and immunomodulatory effects of ibrutinib in combination with trastuzumab in patients with HER2-positive metastatic breast cancer (MBC) whose disease had progressed on ado-trastuzumab emtansine therapy. In Phase I, cohorts of three patients received ibrutinib 560 mg or 420 mg by mouth once daily combined with standard dosing of trastuzumab. Phase II enrolled additional patients to assess the primary endpoint of clinical benefit rate (CBR) at 420 mg ibrutinib plus trastuzumab. Flow cytometry and NanoString analyses were performed on peripheral blood mononuclear cells. Overall, 26 patients were enrolled. Patients received a median of three prior regimens containing a HER2-targeted therapy in any setting. The most common treatment-related adverse events were bruising, rash, fatigue, and thrombocytopenia. Four patients (15%) experienced cardiac adverse events, including decreased left ventricular ejection fraction in two patients. The CBR of ibrutinib plus trastuzumab was 19.2% (95% confidence interval: 6.6-39.4). Flow cytometry of T- and natural killer (NK)-cell and myeloid-cell panels showed that treatment statistically significantly decreased T helper 17 (T_H17) and myeloid-derived suppressor cells (MDSC) with no decrease in T helper 2 (T_H2) cells. Ibrutinib plus trastuzumab was well-tolerated but had limited anti-tumor activity in patients with heavily pretreated, HER2-positive MBC (NCT03379428). Trial Registration: Clinicaltrials.gov, NCT03379428.

Goniothalamin (GTN), a natural styryl-lactone from the Goniothalamus genus, has demonstrated cytotoxic properties against a variety of human cancer cell lines with minimal effects on normal cells. Its traditional medicinal use and preliminary preclinical evidence suggest potential as a selective anticancer agent. The purpose of this review is to summarize the preclinical anticancer activity, molecular mechanisms, and therapeutic potential of GTN and its semi-synthetic derivatives across cancer cell lines and animal models. A comprehensive literature search was conducted on the anticancer effects of GTN using databases including PubMed, Scopus, and ScienceDirect. Studies reporting in-vitro cytotoxicity, half-maximal inhibitory concentration (IC50) values, mechanisms of action, synergistic drug effects, and in-vivo antitumor efficacy were included. Data on GTN enantiomers and semisynthetic derivatives were also analyzed. GTN exhibited potent, dose- and time-dependent cytotoxicity in breast, colorectal, hepatoma, leukemia, and other cancer cell lines (IC₅₀ in the low micromolar range), while sparing normal cells. Mechanistically, GTN induced DNA damage, reactive oxygen species (ROS) generation, cell cycle arrest, endoplasmic reticulum stress, apoptosis, autophagy, necroptosis, and anoikis. The anticancer activity of GTN enantiomers appears to be cell-line dependent: although the (R)-enantiomer showed higher potency in several cancer models, the (S)-enantiomer displayed greater activity in selected cancer cell lines. GTN synergized with chemotherapeutics such as paclitaxel, vinblastine, and cisplatin, enhancing apoptosis and reducing cell viability. Semi-synthetic derivatives, including methoxy- and nitro-substituted analogs, demonstrated enhanced potency and selectivity. In animal models, GTN exhibited antitumor activity without detectable toxicity. GTN is a promising natural anticancer agent with multimodal mechanisms of action and selective cytotoxicity. Semisynthetic derivatives further improve its potency and specificity. Further in-vivo studies, bioavailability, and pharmacokinetic investigations are warranted to advance GTN towards clinical application.

Resistance to immune checkpoint blockade substantially limits its clinical efficacy in head and neck squamous cell carcinoma(HNSCC). ZC3H13 is a component of the N6-methyladenosine writer complex, but its roles in HNSCC progression and response to anti-programmed cell death protein 1(anti-PD-1) therapy remain unclear.

The expression and clinical relevance of ZC3H13 were evaluated using clinical cohorts and publicly available transcriptomic datasets. Gain- and loss-of-function experiments were performed to determine the effects of ZC3H13 on the malignant phenotypes of HNSCC cells. An epithelial-specific ZC3H13 conditional knockout mouse model of 4-nitroquinoline-1-oxide-induced oral tumorigenesis was used to assess tumor development and responsiveness to anti-PD-1 therapy. N6-methyladenosine modification, RNA stability and functional rescue assays were conducted to investigate the underlying molecular mechanism.

ZC3H13 was upregulated in HNSCC and was associated with poor prognosis and a limited response to anti-PD-1 treatment. ZC3H13 promoted the proliferation and invasion of HNSCC cells, whereas epithelial-specific ablation of ZC3H13 suppressed oral tumorigenesis and enhanced the therapeutic efficacy of anti-PD-1 treatment. Mechanistically, ZC3H13 regulated the N6-methyladenosine modification of cyclin D1(CCND1) mRNA and promoted its IGF2BP1-dependent stabilization, thereby contributing to malignant tumor phenotypes and alterations in immunosuppressvie features.

The ZC3H13/IGF2BP1/CCND1 regulatory axis contributes to HNSCC progression and resistance to anti-PD-1 therapy. These findings identify ZC3H13 as a potential therapeutic target for improving the efficacy of anti-PD-1 treatment in HNSCC.

Gastrointestinal (GI) cancers are a leading cause of cancer-related death worldwide, while drug resistance and treatment-related toxicity continue to limit therapeutic efficacy. A growing body of evidence indicates that the gut microbiota-immune axis (GMIA) is closely involved in the development, progression, and treatment response of GI malignancies. In this review, we summarize current understanding of how gut microbial dysbiosis and GMIA dysfunction contribute to GI cancer development and progression. We highlight the role of natural polysaccharides in modulating gut microbial composition and microbial metabolites, thereby influencing host immune responses and exerting antitumor potential in preclinical settings. In addition, we review recent advances in representative natural polysaccharides as promising candidates for the prevention and treatment of gastrointestinal cancers, with an emphasis on their translational prospects and priorities for future investigation.