Prostate cancer is a multifactorial disease influenced by both genetic and environmental factors. Previous studies have identified a correlation between p21 expression and the clinical severity of prostate cancer. However, the contribution of cyclin-dependent kinase inhibitor 1A (CDKN1A), which encodes p21, to prostate cancer susceptibility remains unclear. This study aimed to evaluate the association between CDKN1A polymorphisms rs1801270 and rs1059234 and the risk of prostate cancer in a Taiwanese population.

Tumors with mismatch repair deficiency (MMRd) classically display concomitant loss of MLH1/PMS2 or MSH2/MSH6 on immunohistochemistry (IHC) with microsatellite instability-high (MSI-High) status on molecular testing. Nevertheless, a different phenotype can occur in up to 15% of MMRd tumors (unusual phenotype). Data on the efficacy of immunotherapy in this population remain scarce.

Rare B-rapidly accelerated fibrosarcoma gene (BRAF) mutations in advanced melanoma, and other malignancies, represent a significant clinical challenge due to sparse evidence on the efficiency of targeted therapy. Conventional genomic databases do not integrate detailed outcome data on treatments for patients with these mutations, requiring innovative informatics approaches.For the use case of patients with rare BRAF-mutated melanoma, we developed a "Treatment Outcome Tool" as a web-based database on rare cancers that aggregates anonymized, expert-validated clinical data. Unstructured interviews with dermato-oncologic experts guided the design, ensuring that the system allows users to query specific or combined rare BRAF mutations and retrieve key outcome measures, such as progression-free survival, overall response rate, and disease control rate with BRAF and/or mitogen-activated proteinkinase kinase (MEK) inhibition. Data are collected via a structured input form. After rigorous review and quality assurance by dedicated experts, data are then transferred to an externally accessible R/Shiny platform, where they can be assessed. The usability of the developed database was then evaluated by the System Usability Scale (SUS) of contributing dermato-oncologic experts.The first productive database version was implemented in October 2024. As of May 2025, the database contained data from 130 patients with 23 BRAF mutations. Evaluation of the "Treatment Outcome Tool" by 14 international dermato-oncologic experts yielded a median SUS score of 92.5, confirming excellent usability.Our database fills a critical gap in personalized oncology therapy by directly correlating rare BRAF mutation profiles with treatment outcomes. Our tool had usability and was found to be of high clinical value. The generic informatics framework chosen by us has the potential to be expanded to other rare tumors, ultimately enhancing evidence-based clinical practice and fostering international collaboration in cancer research.

Obesity increases the risk of colorectal cancer (CRC) development, accelerates disease progression and is associated with decreased disease-free survival. Obesity adversely affects the visceral adipose tissue (VAT) leading to increased secretion of extracellular vesicles (EVs). However, the crosstalk between VAT and CRC tumor cells still remains unclear. EVs are lipid-membraned particles that transfer cargo to and/or induce signaling in other cells. Here, we characterized human VAT-derived non-obese (N-OB) and obese (OB) EVs and investigated the functional interaction between CRC cells and VAT-derived EVs. EVs were isolated from VAT obtained from obese (BMI>30) and non-obese patients (BMI<30). Unbiased proteomics revealed that compared to N-OB EVs, OB EVs were enriched with glycolytic enzymes like triose phosphate isomerase (TPI1). This enrichment was associated with increased TPI1 protein levels in CRC cells and elevated glycolytic activity. OB EV-treated cells also exhibited increased stemness-associated genes, 3D-spheroid formation and Apcmin/+ tumoroid self-renewal capacity. In vivo, mice with an adipocyte-specific knockout of EV cargo sorting protein, Tsg101 (Tsg101ΔAd), had altered EV cargo composition with reduced glycolytic enzyme levels. Functionally, Tsg101ΔAd-EVs were able to protect against high-fat diet (HFD)-induced increase in glycolysis and stem-like ability. Moreover, Apcmin/+:Tsg101ΔAd mice were protected against HFD-induced enhanced tumorigenesis. Collectively, this study identifies adipocyte EVs, and their metabolic cargo, as an important regulator of CRC cell metabolism and function, promoting intestinal tumorigenesis.

Osteosarcoma (OS) is a highly aggressive bone cancer with complex molecular mechanisms and variable patient outcomes. This study delineates the paraptosis-related genes (PRGs) landscape in OS and its association with prognosis and the immune microenvironment using bioinformatics approaches. Sixty PRGs were identified and annotated in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and GSE21257 cohorts. Consensus clustering stratified patients into molecular clusters, revealing significant survival differences. A risk score was developed using LASSO-Cox regression, which effectively stratified patients into high and low-risk groups. Immune profiling revealed significant differences in immune cell infiltration, with high-risk groups exhibiting decreased levels of activated immune cells. Pathway enrichment analysis indicated higher activity in WNT/BETA-CATENIN, TGF-BETA, and KRAS signaling pathways in high-risk groups. Single-cell RNA sequencing highlighted elevated TNK2 expression in malignant cells. Functional assays confirmed TNK2's role in cell proliferation, viability, and migration, and showed that TNK2 knockdown mitigated cycloheximide-induced proliferation inhibition, linking TNK2 to paraptosis regulation. These findings identify key PRGs and their prognostic significance in OS, revealing distinct immune microenvironments and signaling pathways between molecular clusters. This study also underscores the importance of TNK2 in OS pathogenesis and its potential utility in developing personalized treatment strategies.

Over the past decades, significant advancements have been made in various medical fields; however, ovarian cancer (OC) remains inadequately addressed, predominantly relying on relatively toxic cytostatic treatments. In this study, we applied newly developed poly(β-amino) esters (PBAEs) for siRNA delivery. As recent literature has shown, the introduction of a hydrophobic, unsaturated fatty acid together with polycationic spermines as the PBAE side chains are leading to a favourable transfection efficiency, and the resulting materials form a unique class of micelleplexes, termed micelle-embedded polyplexes (mPolyplexes). Here, such mPolyplexes were modified post-particle formation with the approved monoclonal antibody Trastuzumab for HER2 targeting, as supported by a receptor binding analysis through fluorescence shift assay. Physicochemical analysis revealed suitable hydrodynamic diameters of modified mPolyplexes, as determined by dynamic light scattering. Improved cellular uptake when targeted with Trastuzumab was optimized by applying Design of Experiment (DoE). We demonstrated superior gene silencing efficiency of EGFR as well as PLK1, both involved in OC progression, with knockdown values exceeding 82% and 70%, respectively. These findings were corroborated by a relevant cell migration assay. The macroscopic impact after PLK1 silencing on epithelial-mesenchymal transition (EMT) was visualized using confocal microscopy. This work addresses critical questions in the field of ovarian cancer therapy and confirms the suitability of siRNA encapsulating PBAE nanocarriers as promising non-viral vectors.

Measurable residual disease (MRD) is a key predictor of relapse, the primary cause of treatment failure after allogeneic haematopoietic cell transplantation (allo-HCT) in acute myeloid leukaemia. This Policy Review, based on guidance from the European Society for Blood and Marrow Transplantation, provides practical recommendations for incorporating MRD assessment into clinical decision making during the transplantation process, the application of which remains challenging in acute myeloid leukaemia due to technical limitations and the limited availability of standardised, evidence-based approaches. Available methods include reverse transcription quantitative PCR, digital droplet PCR, next-generation sequencing, and multiparametric flow cytometry-chimerism-based approaches are under investigation. This Policy Review highlights the importance of MRD monitoring to enable timely, risk-adapted interventions that encompass both pre-transplantation and post-transplantation periods and can include tailoring conditioning intensity, donor selection, immunosuppression management, donor lymphocyte infusions, and pharmacological therapies such as FLT3 or IDH inhibitors, hypomethylating agents, venetoclax, or menin inhibitors. These recommendations aim to harmonise MRD-driven clinical practice and improve patient outcomes, while identifying key areas for future research.

Advances in cancer immunotherapy from immune checkpoint modulation to adoptive cell transfer of tumour-infiltrating lymphocytes (TILs) have greatly improved outcomes for patients with advanced cancers, particularly metastatic melanoma. The approval of TIL therapy in 2024 following two independent landmark clinical trials has established this approach as a viable treatment option, with response rates of up to 50% in treatment-resistant melanoma. Genetic engineering offers new opportunities to further improve TIL efficacy and durability, including viral vector-mediated overexpression of cytokines or chimeric receptors, and non-viral genome editing techniques such as CRISPR-Cas9 to delete inhibitory genes such as PD-1 and CISH. In this Review we outline the current state of genetically engineered TILs, highlighting both preclinical advances and ongoing clinical trials. As these engineered products are evaluated in clinical settings, they are expected to expand the personalised immunotherapy toolkit and improve durable outcomes across a broader range of solid tumours.

Patritumab deruxtecan (HER3-DXd) is a novel antibody-drug conjugate targeting HER3, which is overexpressed in CNS metastases of advanced non-small-cell lung cancer (NSCLC). We aimed to evaluate the activity and safety of HER3-DXd in patients with advanced NSCLC and newly diagnosed brain metastases or brain metastases progressing after local therapy.

A biological transition from a state N to a state T is marked by a rearrangement of the gene expression profile in the system, quantitatively measured through the differential expression of genes. In contrast, changes in genetic pathways are usually evaluated by means of hypothesis testing schemes.

Cancers, especially fusion oncoprotein (FO)-driven hematological cancers and sarcomas, often develop from a low number of key mutations. Solitary Fibrous Tumor (SFT) is a rare mesenchymal tumor driven by the NAB2-STAT6 oncofusion gene. Currently, the treatment options for SFT remain limited, with anti-angiogenic drugs providing only partial responses with an average survival of two years. We constructed SFT cell models harboring specific NAB2-STAT6 fusion transcripts using the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology, and we used these cells as models of SFT. High-throughput drug screens demonstrated that the BET inhibitor Mivebresib can differentially reduce proliferation in SFT cell models. Subsequently, BET inhibitors Mivebresib and BMS-986158 efficiently reduced tumor growth in an SFT patient-derived xenograft (PDX) animal model. Furthermore, our data showed that NAB2-STAT6 fusions may lead to high levels of DNA damage in SFTs. Consequently, combining BET inhibitors with PARP (Poly (ADP-ribose) polymerase) inhibitors or with ATR inhibitors significantly enhanced anti-proliferative effects in SFT cells. Taken together, this study establishes BET inhibitors Mivebresib and BMS-986158 as promising anti-SFT agents.

Quantifying changes in circulating tumor DNA (ctDNA) during treatment can rapidly identify patients responding to therapy, but accurate interpretation requires an understanding of variability in ctDNA levels in the absence of treatment. This analysis of 360 patients with advanced epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) characterized ctDNA level changes in paired pretreatment samples and evaluated factors associated with variability.

Salivary gland cancers (SGCs) are rare and comprise multiple histologic entities. In the recurrent or metastatic (R/M) setting, there is limited evidence for effective systemic anticancer treatment for most subtypes, affecting prognosis and quality of life. Molecular analysis of SGCs holds promise to more accurately classify SGC subtypes and to determine novel therapeutic targets.

CNS tumors are a significant cause of death in the adolescent and young adult (AYA; age 15-39 years) population; however, these patients often lack standardized treatments.

Translocation-associated sarcomas (TASs) encompass a wide spectrum of pathologic entities and clinical behavior. Driven by the oncogenic fusion, TASs typically show a stable genome and a low tumor mutational burden (TMB), with infrequent secondary genetic alterations (SGAs). Although oncogenic/likely oncogenic SGAs have been associated with an aggressive clinical course in certain histotypes, a comprehensive comparative study of their clinical impact across TAS histotypes has not been performed to date.

Precision oncology trials have generally focused on tumor testing to identify actionable alterations. The National Cancer Institute-Children's Oncology Group Pediatric MATCH trial incorporated return of germline results to assess feasibility of reporting in a cooperative group setting and characterize germline cancer predisposition in patients with refractory cancers.

Multiple myeloma (MM) with extramedullary disease (EMD) represents a subgroup with particularly poor prognosis. The application of precision medicine principles, especially targeted therapy based on the tumor's molecular profile, is a potentially effective treatment strategy.

Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disorder characterized by an extreme lifetime risk of multiple and early-onset tumors, driven by inherited pathogenic variants in the TP53 gene. While somatic mutations in TP53 are among the most frequent genetic alterations in cancer, germline mutations remain rare. Although LFS has long been recognized as a prototypical cancer predisposition syndrome, recent advances have significantly reshaped its diagnostic criteria and deepened our understanding of its associated cancer risks.

BackgroundMelanoma represents one of the most aggressive skin cancers, responsible for over 75% of skin cancer-related deaths despite comprising only 5% of cases. Despite therapeutic advances, patient responses remain variable and unpredicv. The Signaling Lymphocytic Activation Molecule (SLAM) family regulates immune cell communication, with SLAMF8 being predominantly expressed on myeloid cells. However, SLAMF8's specific role in melanoma pathogenesis remains largely unexplored.MethodsIn this retrospective integrative study, we systematically investigated SLAMF8's role in melanoma through multi-omics analyses using TIMER, GEPIA, and UALCAN databases, following the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines for observational data reporting. Functional studies were conducted in A-375 and SK-MEL-28 melanoma cell lines using siRNA-mediated knockdown, followed by migration, invasion, and proliferation assays. DNA methylation patterns were analyzed via the SMART database, while mutation profiles were examined using cBioPortal and COSMIC. Immune infiltration analysis was performed through TIMER, and pathway associations were investigated using Gene Set Enrichment Analysis and protein-protein interaction networks. Finally, two-sample Mendelian Randomization analysis assessed the causal relationship between SLAMF8 expression and melanoma susceptibility.ResultsSLAMF8 expression was significantly higher in metastatic melanoma compared to primary tumors, with expression patterns varying across disease stages and between sexes. Higher SLAMF8 expression correlated with improved disease-free and overall survival. Functional studies demonstrated that SLAMF8 knockdown significantly enhanced melanoma cell proliferation, migration, and invasion. DNA methylation analysis revealed significant negative correlations between methylation at specific CpG sites and SLAMF8 expression, with hypermethylation associated with worse survival outcomes. Mutation analysis identified alterations in 10.21% of melanoma patients. Immune infiltration studies demonstrated strong correlations between SLAMF8 expression and enhanced immune cell presence. GSEA linked SLAMF8 to critical immune pathways including allograft rejection, inflammatory response, and interferon signaling. Mendelian Randomization analysis established a protective causal relationship between SLAMF8 and melanoma risk (OR = 0.39, 95% CI = 0.21-0.74, p = 3.34e-03).ConclusionOur study demonstrates that SLAMF8 plays a critical role in melanoma by suppressing tumor progression and modulating the immune microenvironment. Elevated SLAMF8 expression in metastatic melanoma is associated with improved patient survival, suggesting its utility as a prognostic biomarker. Furthermore, its tumor-suppressive effects and immune-regulatory functions highlight SLAMF8 as a promising therapeutic target for melanoma treatment strategies.

Colorectal cancer (CRC) is a common malignant tumor of the digestive tract, and chemotherapy resistance along with adverse reactions during treatment present significant challenges in clinical practice. Therefore, there is an urgent need to find effective and low-toxicity therapeutic agents. Ferroptosis, a recently discovered form of cell death, has attracted attention as a potential new cancer treatment strategy. Microwave dynamic therapy (MWDT), as a promising anticancer agent, has been shown to significantly inhibit various malignancies, including CRC. However, the role of MWDT in ferroptosis and its underlying mechanisms have not been fully explored. In this study, we demonstrated that MWDT treatment significantly increased levels of lipid peroxidation (LPO), reactive oxygen species (ROS), malondialdehyde (MDA), and Fe2⁺, while significantly decreasing glutathione (GSH) levels. Ferrostatin-1 partially inhibited these effects. Further research revealed that MWDT effectively inhibited tumor growth both in vitro and in vivo by inducing ferroptosis. At the molecular level, overexpression of PTK2B reversed the ferroptosis induced by MWDT. PTK2B interacted with STAT3 and enhanced its phosphorylation at Tyr705, promoting the nuclear translocation of p-STAT3 (Tyr705). In the nucleus, p-STAT3 bound to the GPX4 promoter region and promoted GPX4 transcription. MWDT inhibited PTK2B expression, suppressed STAT3 phosphorylation, and subsequently downregulated GPX4 transcription, thereby inducing ferroptosis. Our findings are the first to demonstrate that MWDT mediates ferroptosis in CRC via the PTK2B/STAT3/GPX4 axis, offering novel theoretical insights for its comprehensive treatment.