Background: Esophageal squamous cell carcinoma (ESCC) is a highly aggressive cancer with a poor prognosis, where immune evasion plays a central role in tumor progression and resistance to therapy. The underlying mechanisms of tumor-stroma interactions remain poorly understood, despite the relationship between epithelial-mesenchymal transition (EMT) and altered immune response having been suggested. This study aimed to investigate how phenotypic shifts in ESCC tumor cells contribute to immune modulation. Methods: We used multiplex immunofluorescence on 4-nitroquinoline 1-oxide (4-NQO)-induced multistage mouse ESCC models to characterize the local tumor microenvironment. Additionally, we integrated multiomics datasets, including spatial transcriptomics, single-cell RNA sequencing, and proteomics, from multistage human esophageal samples to investigate the underlying molecular mechanisms. These findings were further validated through in vitro cell line experiments and in vivo therapeutic models. Results: We identified an ESCC cell cluster with ectopic expression of CD11c (also known as integrin alpha X), in both mice and humans, probably formed via tumor protein p53 (TP53) inactivation, causing cancer cells to escape immune killing and gain malignant phenotypes. CD11c impaired cancer cell antigen presentation and fostered EMT through up-regulation of mothers against decapentaplegic homolog 3 (SMAD3) phosphorylation in human ESCC cell lines. Mechanistically, CD11c activated SMAD3 to suppress costimulatory factors CD80/CD86 and augmented immunosuppressive CD4⁺ T cell responses through aberrant major histocompatibility complex class II-mediated antigen presentation. Evaluation in humanized mouse models further confirmed that CD11c overexpression in ESCC resulted in immune evasion, tumor metastasis, and resistance to anti-programmed death ligand 1 (PD-L1) therapy, but could be rescued by combined treatment with anti-phospho-SMAD3. Conclusions: This study reveals a mechanism by which ectopic CD11c expression causes immunosuppression and contributes to the acquisition of malignant phenotypes in ESCC. Targeting the CD11c-SMAD3 axis may enhance the efficacy of existing immunotherapies, potentially improving the treatment outcomes of ESCC patients.

Sturge-Weber syndrome (SWS) is a sporadic, progressive, congenital condition that occurs due to hamartomatous malformation and is usually referred to as a "port wine stain." It is characterized by trisymptomatic forms that include facial port wine stain, glaucoma, and leptomeningeal calcifications.

A 42-year-old female patient presented with a chief complaint of missing teeth in the mandibular anterior region that had recently exfoliated following mobility. A unilateral port wine stain noted on the left side of her face appeared to follow the left maxillary division of the trigeminal nerve with minimal intraoral signs. The patient claimed it had been present since birth.

The origin, pathophysiology, clinical presentation, differential diagnosis, potential therapies, and prognosis of SWS are discussed.

A multidisciplinary approach to individuals with SWS is required for the successful treatment of these patients.

Collision medullary and papillary thyroid carcinoma (MTC/PTC) is a rare entity, constituting less than 1% of all thyroid malignancies. The concurrent presence of these malignancies in patients with autoimmune thyroid disease, such as Graves' disease, is even more uncommon. Calcitonin (Ctn) is considered one of the key MTC biomarkers. Mixed tumors may alter this relationship.

We report the case of a 55-year-old female with a history of Graves' disease, who underwent total thyroidectomy for persistent dysthyroid orbitopathy. Histopathological analysis revealed a 9-mm collision MTC/PTC tumor in the left thyroid lobe, confirmed through immunohistochemical staining. Postoperative evaluation demonstrated lymph node metastases, necessitating central and left lateral neck dissection. Postoperative serum markers (calcitonin, carcinoembryonic antigen, thyroglobulin) declined significantly following surgery and radioiodine therapy.

Subcentimeter collision MTC-PTC tumors can be aggressive, challenging size-based management thresholds. Treatment should integrate MTC and PTC protocols, with Ctn, carcinoembryonic antigen (CEA), and thyroglobulin monitored in tandem. Larger datasets are needed to refine Ctn prognostic thresholds in mixed tumors.

Hepatitis C virus (HCV) and hepatitis B virus (HBV) infections are increasingly recognized as significant etiological factors in the pathogenesis of B-cell non-Hodgkin's lymphomas (B-NHLs). Epidemiological and molecular studies have demonstrated a consistent association between chronic viral infection and B-NHLs. Multiple pathogenic mechanisms have been implicated in lymphomagenesis, both direct and indirect, including chronic antigenic stimulation, direct infection of B cells, and viral protein-mediated oncogenic signaling, It is likely that a combination of several pathogenic conditions is required to eventually lead to the development of lymphoma. The prevalence of B-cell lymphomas among individuals with chronic HCV or HBV infection presents a complex pathogenetic scenario, given the tumor heterogeneity and variable clinical behavior, and poses therapeutic challenges, due to the partial efficacy of current treatment options. The advent of direct-acting antivirals (DAAs) for HCV and high-genetic barrier nucleos(t)ide analogues (NAs) for HBV has improved patient outcomes. In indolent HCV-associated B-NHLs, antiviral therapy with DAAs alone often achieves sustained virologic response and may lead to lymphoma regression. Conversely, aggressive subtypes like diffuse large B-cell lymphomas require combination treatment with immunochemotherapy. In the setting of HBV-associated lymphomas, antiviral prophylaxis with potent NAs (e.g., entecavir or tenofovir) is essential to prevent HBV reactivation during rituximab-containing chemotherapy regimen. The integration of antiviral and anticancer therapies has been shown to enhance survival outcomes while mitigating hepatic toxicity. A comprehensive understanding of the biological interplay between chronic viral infection and B-cell transformation is critical for optimizing diagnostic and therapeutic strategies. Aim of this viewpoint is to provide evidence that early viral detection and prompt management remain the most effective strategies to improve survival rates and to reduce treatment-related morbidity in these patients.

The five-year survival rate for pancreatic cancer is notably low, posing a significant challenge to patient health. The primary treatments are radiotherapy and chemotherapy, sometimes combined with targeted therapy; however, their clinical benefits are limited. Therefore, developing new models to evaluate the therapeutic potential of novel molecules is essential. Fingolimod and Dimethyl Fumarate (DMF), currently used to treat multiple sclerosis, have recently been shown to have anti-cancer effects in several preclinical tumor models. This study aims to evaluate the therapeutic potential of Fingolimod and DMF in pancreatic cancer by investigating their respective in vitro cytotoxicity and in vivo antitumor effects.

In this study, we evaluated for the first time these two drugs in pancreatic preclinical models in vitro using 3D spheroid tumor models and in vivo, which are compared to two standard-of-care consisting of Gemcitabine and Erlotinib.

In vitro, both Fingolimod and DMF induced cytotoxicity in spheroids from two pancreatic cell lines. Additionally, Fingolimod and DMF displayed anticancer effects in two subcutaneous xenograft models using PANC-1 and CFPAC-1 cells.

Although the responses observed with Fingolimod and DMF were similar to those of Gemcitabine and Erlotinib, these findings indicate a potential emerging interest in Fingolimod and DMF for the treatment of pancreatic cancer. However, further work is still necessary to fully characterize how these drugs affect tumor progression.

Prostate cancer (PCa) is the most prevalent malignancy in men and often correlates with distant metastasis in its advanced stages. The study aimed to investigate the effects of Ugonin J, a natural compound isolated from Helminthostachys zeylanica, on PCa metastasis.

The effects of Ugonin J on cell motility were assessed using migration and invasion assays. Reverse Transcription Quantitative PCR (RT-qPCR) and Western blotting were used to evaluate the impact of Ugonin J on mRNA and protein expression. RNA sequencing (RNA-seq) analysis was performed to investigate candidate mechanisms. Differential gene expression analysis in PCa patients was conducted using multiple databases.

Here, we reveal that Ugonin J blocks migration and invasion in PCa cells without affecting cell viability. RNA-seq analysis suggests that epithelial-mesenchymal transition (EMT) is potentially involved in Ugonin J's anti-motility effects. Ugonin J also suppresses the expression of mesenchymal markers N-cadherin, β-catenin, Snail, and Slug while upregulating the expression of the epithelial marker E-cadherin. Furthermore, among 13 A disintegrin and metalloproteinase (ADAM) proteins, A disintegrin and metalloproteinase domain-containing protein 9 (ADAM9) is the most downregulated following Ugonin J treatment, according to our RNA-seq data. Importantly, clinical data revealed that ADAM9 expression are higher in PCa patients than in healthy controls and are associated with distant metastasis. Transfection with ADAM9 cDNA reverses Ugonin J-regulated downregulation of EMT, migration, and invasion in PCa cells. Ugonin J inhibits ADAM9-dependent motility by downregulating the phosphoinositide 3-kinase (PI3K), protein kinase B (Akt) and nuclear factor-κB (NF-κB) pathways.

Our evidence suggests that Ugonin J is a novel therapeutic candidate for further development as a treatment for metastatic PCa.

Tumor survival, genomic stability, and therapy resistance are dictated by the DNA damage response (DDR). Although poly (ADP-ribose) polymerase (PARP) inhibitors have established the DDR as a therapeutic target, many tumors evade first-generation drugs by rewiring their adaptive repair pathways and imposing microenvironmental constraints. This review synthesizes recent discoveries in key DDR pathways, such as PARP, ataxia telangiectasia and Rad3-related kinase (ATR), ataxia telangiectasia mutated kinase (ATM), checkpoint kinase 1 (CHK1), WEE1 G2 checkpoint kinase (WEE1), and DNA-dependent protein kinase (DNA-PK), and describes the next-generation inhibitors designed to increase selectivity and circumvent resistance. We also analyze the role of hypoxia, stromal remodeling, inflammatory cytokines, and immune-cell plasticity in the tumor microenvironment in determining DDR dependency and response. Special attention is paid to cGAS-STING, immunogenic signaling via damage-associated molecular patterns (DAMPs), and mechanisms that convert a cold tumor into a hot one. Lastly, we touch upon the new nanocarrier-based delivery approaches that enhance pharmacokinetics, target resistant tumor niches, and expand the possibilities for combinatorics with immunotherapy and radiotherapy. Collectively, these findings provide a guide to the implementation of next-generation DDR inhibitors and nanomedicines to deliver a more accurate, durable, and context-specific cancer therapy.

Skin cancer remains the most commonly diagnosed malignancy worldwide, with basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and melanoma representing the most clinically significant types. While traditional treatments are effective for early-stage disease, advanced or metastatic cases often pose significant therapeutic challenges. Patients with high-risk or recurrent disease face limited options and poor prognoses. The emergence of immunotherapy has dramatically transformed the treatment landscape across multiple cancer types, including cutaneous malignancies. This review highlights recent advancements in immunotherapeutic strategies for BCC, cSCC, and melanoma, underscoring their growing importance in dermatologic oncology. We synthesize current evidence and ongoing clinical trials for immunotherapy across these three skin cancer types. We also explore the molecular mechanisms underpinning immune responsiveness and potential biomarkers of response. As immunotherapy continues to expand within dermatology, understanding its role, limitations, and future directions is essential for optimizing patient care. The integration of immunotherapy into dermatologic practice represents not only a therapeutic innovation but also a shift toward precision medicine in cutaneous oncology.

Acute myeloid leukemia (AML) remains a biologically heterogeneous disease with historically limited targeted therapies and poor outcomes. The development of menin inhibitors represents a promising shift, particularly for patients harboring KMT2A rearrangements (KMT2Ar) and NPM1 mutations (NPM1m). This manuscript reviews the molecular rationale of menin inhibition for aberrant homeobox/myeloid ectopic insertion site 1 (HOX/MEIS1)-driven gene expression and leukemogenesis, clinical trial outcomes, and safety data for menin inhibitors, with a focus on recently FDA-approved revumenib and several other agents in development, ziftomenib (KO-539), bleximenib (JNJ-75276617), and icovamenib (BMF-219). We also focused our discussion on future directions to include resistance mechanisms, biomarker identification and monitoring strategies, and combination therapies. Menin inhibition is now being clinically integrated into relapsed/refractory and frontline treatment settings.

Phosphodiesterase 1A (PDE1A) regulates intracellular cyclic nucleotide signaling and has been implicated in tumor progression, but its clinical relevance and functional role in epithelial ovarian cancer (EOC), particularly in relation to the response to platinum remain unclear. This study aimed to evaluate the clinical significance of PDE1A in EOG and to clarify its functional role in tumor progression and response to platinum-based chemotherapy.

PDE1A mRNA and protein levels were analyzed using public databases, RNA sequencing, and immunohistochemistry. Correlations between PDE1A expression, clinicopathological features, and prognosis were assessed. Functional roles were investigated in ovarian cancer cell lines.

PDE1A was significantly overexpressed in EOC tissues compared with that in normal ovarian epithelial tissues. Overexpression correlated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, poor tumor grade, and reduced response to platinum-based chemotherapy. High PDE1A levels were linked to worse disease-free survival and overall survival, and multivariate analysis confirmed PDE1A as an independent prognostic factor. To elucidate its functional role, we performed in vitro experiments showing that PDE1A knockdown suppressed cell proliferation and colony formation, induced G1 arrest, and downregulated β-catenin signaling with reduced cyclin D1 and c-Myc expression. Notably, these inhibitory effects were partially rescued by lithium chloride (LiCl), a Wingless-related integration site (Wnt)/β-catenin activator.

In conclusion, our findings identify PDE1A as a Wnt/β-catenin-linked biomarker of tumor progression and platinum resistance in EOC and provide a biological rationale for further investigation of PDE1A-targeted strategies in preclinical models.