Prostate magnetic resonance imaging (MRI) has become a crucial tool in diagnosing and managing prostate cancer, mainly by helping to avoid unnecessary biopsies and enhancing the detection of clinically significant disease. However, its clinical usefulness is often limited by wide variation in how images are acquired, interpreted, and reported worldwide. This inconsistency affects diagnostic accuracy and patient outcomes. In response, the Quality Improvement Subgroup of the European Society of Urogenital Radiology (ESUR) Prostate MRI Working Group has created a practical, three-step quality-improvement framework aimed at standardising and improving prostate MRI practices. This framework consists of: Step 1: 'Build it right', establishing a foundation of technical excellence through adherence to the Prostate Imaging Reporting and Data System (PI-RADS) technical standards, objective quality assessment using the Prostate Imaging Quality (PI-QUAL) score, and systematic artefact reduction. Step 2: 'See it right', emphasising interpretive excellence via structured training, institutional quality assurance metrics, and multidisciplinary collaboration. Step 3: 'Improve and innovate', promoting continual refinement through emerging technologies such as AI-driven assessment, deep learning reconstruction, and remote supervision. By incorporating this structured approach into daily practice, this framework aims to ensure that prostate MRI consistently fulfils its promise of accurate, reproducible, and patient-centred care. A coordinated effort towards international implementation, benchmarking, and outcome-based validation represents the next critical step to maximise global impact. KEY POINTS: Question Wide variation in prostate MRI acquisition, image quality, and reporting undermines diagnostic accuracy. A structured roadmap is needed to ensure consistent quality and reproducible practice. Findings The ESUR Prostate MRI Working Group outlines a three-step framework - 'Build it right', 'See it right', 'Improve and innovate' - to standardise acquisition, interpretation, and quality assurance. Clinical relevance Applying this roadmap in clinical practice aims to enhance diagnostic confidence and promote consistent, high-quality prostate cancer care across diverse healthcare settings.

To evaluate the technical and clinical outcomes of percutaneous metallic stenting in patients with malignant bilioenterostomy obstruction and to identify risk factors affecting stent patency.

This retrospective study included 368 patients (240 men, 128 women; mean age, 68.2 years; range, 39-95 years) who underwent percutaneous biliary metallic stent placement between March 2012 and November 2023. Patients were categorized into three groups based on stent type: covered, single uncovered, and double uncovered.

Technical success was achieved in all patients. Uncovered stents-single uncovered (n = 208; 56.5%) and double uncovered (n = 50; 13.6%)-were placed in 70.1% of patients, while covered stents were used in 29.9%. Major and minor complication rates were 1.1% and 1.9%. Successful internal drainage, defined as removal of the temporary drainage catheter, was achieved in 87.8% of patients. Median survival and stent patency times were 241 days (95% CI, 216-266) and 255 days (95% CI, 194.7-315.3). No significant factors were associated with overall survival. Stent occlusion occurred in 50.5% of patients, most commonly due to tumor ingrowth (74.3%). On multivariate Cox regression, double uncovered stent placement (HR, 0.440; 95% CI, 0.295-0.656; p < 0.001), covered stent placement (HR, 0.301; 95% CI, 0.161-0.564; p < 0.001), and post-stenting serum bilirubin < 2.0 mg/dL (HR, 0.715; 95% CI, 0.517-0.990; p = 0.043) were independent predictors of prolonged stent patency.

Percutaneous metallic stenting is a safe and effective treatment for malignant bilioenterostomy obstruction. Covered and double-uncovered stents are associated with longer stent patency.

Question: What are the technical and clinical outcomes of percutaneous metallic stenting in malignant bilioenterostomy obstruction, and which factors affect stent patency?

Covered and double-uncovered stents showed significantly longer patency. Stent type and bilirubin < 2.0 mg/dL were independent predictors of patency.

Percutaneous metallic stenting is safe and effective for malignant bilioenterostomy obstruction. Covered and double uncovered stents prolong patency, supporting their use as preferred options to improve long-term biliary drainage and patient outcomes.

High‑dose methotrexate (HD‑MTX) is a cornerstone of pediatric acute lymphoblastic leukaemia (ALL) therapy. However, deviations from protocol-mandated infusion durations need regular monitoring as part of standard quality care. Hence, an observational quality assessment study was planned with a secondary objective to evaluate the acute toxicity in patients who did not receive the infusion within the recommended time period.

This study enrolled 42 children (75 cycles) who received HD-MTX (3-5 g/m² over 24 h) according to the ICiCLe ALL-14 protocol. The actual infusion duration was recorded, and 48-h MTX levels were measured using an enzyme-multiplied immunoassay technique. Toxicity was graded via CTCAE v5.0.

Only 35% of cycles were completed within the targeted 24-h window [Median (IQR): 23.75 h (21.25, 25.33)]. Prolonged infusions (> 25 h) resulted in significantly higher 48-h MTX levels compared to shortened infusions (median 0.475 vs 0.270 µmol/L; p = 0.015). Multivariable analysis identified male sex (OR, 12.24), T-ALL immunophenotype (OR, 8.36), and the infusion duration (OR, 1.50 per hour) as independent predictors of delayed clearance. A 48-h level > 0.315 µmol/L predicted development of toxicity (AUC 0.686), though no life-threatening event or mortality was recorded in any cycle. Additionally, MTX levels did not differ significantly across the four HD-MTX cycles that each patient received, and elevated levels in one cycle did not predict delayed clearance in subsequent cycles.

Deviations in infusion duration were high and independently drive pharmacokinetic variability and toxicity. Ensuring timely drug delivery is as critical as dose precision.

Colorectal cancer (CRC) constitutes a prominent global health burden, being the third most frequently diagnosed malignancy in terms of incidence and the second leading cause of cancer-associated death across the globe. Malignant transformation of colonic epithelial cells stems from the intricate dysregulation of intracellular signal transduction networks. Although targeted therapies have substantially improved patient survival relative to traditional treatments, the complexity of the molecular networks driving carcinogenesis continues to limit the overall prognosis. This review delineates the core signaling cascades governing CRC initiation and progression, with emphasis on the molecular hallmarks of the disease. Drawing on a growing body of high-quality preclinical and clinical evidence, we summarize currently available targeted agents and critically evaluate their underlying mechanisms of action and clinical curative effects, and inherent limitations within the contemporary therapeutic landscape. In addition, we discuss how recent advances in immune checkpoint inhibitors (ICIs) along with a deeper understanding of the tumor microenvironment are shaping global clinical guidelines and revealing promising new targets and combinatorial strategies. In summary, expanding insights into oncogenic signaling pathways are guiding the development of novel treatments and enabling the identification of key elements amenable to pharmacological intervention. Ultimately, this review aims to support the rational design of precise and personalized therapeutic strategies to improve CRC prognosis.

The proteasome inhibitor bortezomib and purine nucleoside analog clofarabine combination had greater than additive activity in the NCI-ALMANAC preclinical screen. We conducted a phase 1 trial (NCT02211755) to evaluate the combination's safety and efficacy in patients.

We administered bortezomib subcutaneously on days 1 and 4, and clofarabine intravenously on days 1-5 of each 21-day cycle. The primary objective was to establish the safety, tolerability, and maximum tolerated dose (MTD) of bortezomib and clofarabine in patients with refractory solid tumors, lymphomas, or MDS. The secondary objective was to determine the effects of the combination on biomarkers of cell death and DNA damage response (DDR) in tumor biopsies.

Of 28 patients enrolled, 11 had a best response of stable disease (median 5 cycles; range 2-10 cycles), including 5 patients (4 from the solid tumor cohort, 2 of which were at MTD) with stable disease for ≥ 6 cycles. The MTD for the solid tumor cohort was 1.3 mg/m² bortezomib on days 1 and 4, and 1.5 mg/m² clofarabine on days 1-5 of each cycle. The MDS cohort closed prior to MTD determination, due to low accrual. The most common study drug related adverse events were hematologic. Two out of 3 patients with evaluable biopsies had increased markers of cell death, and 1 patient also had increased DDR markers after treatment.

The combination of bortezomib with clofarabine demonstrated limited antitumor effects possibly due to the inability to reach the efficacious doses achieved in preclinical models.

By blocking poly ADP ribose polymerase (PARP), olaparib decreases the proliferation of tumours by preventing DNA damage repair, particularly in tumours that have BRCA1/2 mutations or are BRCA-negative. However, a phase II study of 33 CRC patients receiving mono-olaparib therapy revealed that some of these individuals still had resistance to olaparib therapy but had poor DNA damage repair ability. RAD51C reversion mutation is a frequent reason for the resistance of cancers with BRCA mutations to PARP inhibitors.

Here, we introduce K(lysine)-acetyltransferase 2B (KAT2B) as a protein involved in the transcription of RAD51C, reducing the expression of RAD51C by lowering the acetylation of histone H3 (H3K27) at the promoter of RAD51C.

We found that a subset of tumour cells expressing RAD51C presented reduced endogenous KAT2B expression, which led to increased accumulation of DNA damage (increased γH2AX accumulation), and lower KA2TB expression decreased PARPi resistance in RAD51C-expressing cells. These findings indicate that colorectal cancer cells with lower KAT2B and RAD51C levels are more vulnerable to olaparib therapy. Our findings indicate that PARPi responses and the expression of RAD51C are significantly regulated by KAT2B and histone acetylation.

These results offer vital and novel insights into the combination of inhibitors in patients who are resistant to olaparib therapy, especially patients with RAD51C reversion mutations.

Chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapies have demonstrated remarkable efficacy in hematologic malignancies; however, their clinical performance in solid tumors remains limited due to suboptimal tumor infiltration, antigen heterogeneity, and immunosuppressive tumor microenvironments (TME). Invariant natural killer T (NKT) cells have recently emerged as a promising alternative platform for CAR engineering, owing to their intrinsic tissue-homing capacity, multi-modal cytotoxicity, and ability to reshape the TME. In this study, we performed a comprehensive preclinical comparison of conventional CAR-T cells and allogeneic stem cell-derived IL-15-enhanced CAR-NKT cells in solid tumor models, integrating spatiotemporal transcriptomic profiling across multiple tissues and longitudinal time points. Our analyses revealed distinct in vivo pharmacokinetic, pharmacodynamic, and immunoregulatory profiles between the two cell therapy modalities. Compared with CAR-T cells, CAR-NKT cells demonstrated superior homing, infiltration, and localization within solid tumors, along with prolonged in vivo persistence and a unique immune checkpoint receptor expression landscape. Notably, CAR-T cells exhibited synergistic antitumor responses when combined with TIGIT blockade, whereas CAR-NKT cells showed greater sensitivity to CD96 blockade in vivo. These findings highlight the divergent therapeutic dynamics of CAR-T and CAR-NKT cells and provide mechanistic insights that inform the rational design of next-generation cell therapies and combinatorial strategies for solid tumors.

SUMO-specific peptidase 3 (SENP3), as a de-SUMOylating enzyme, renders the process of protein SUMOylation reversible. It has been demonstrated to play either promoting or inhibitory roles in several cancers. However, research on its function in colorectal cancer (CRC) remains absent.

Tissue samples from CRC patients were analyzed to measure the expression level of SENP3. Proliferation and viability assays were performed to assess the role of SENP3 in cell growth. The mouse model was established to evaluate the effect of SENP3 on the growth of xenografts derived from CRC cells. To investigate the mechanisms of SENP3 in CRC, proteomic analysis was conducted.

We identified an elevated expression of SENP3 in cancerous tissues, which correlated with a reduced survival rate in CRC patients. SENP3 promoted cell growth in vitro and boosted tumorigenicity in vivo as a potential oncogenic factor. In terms of mechanism, proteomic analysis revealed that growth differentiation factor 15 (GDF15) is a downstream effector of SENP3. Treatment with MG132 confirmed that SENP3 enhances the stability of GDF15. Through a series of cellular functional experiments and mouse model establishment, we demonstrated that SENP3 regulates CRC progression by acting on GDF15.

Based on our findings, we define a key role for SENP3 in colorectal cancer progression and suggest it as a viable target for therapeutic intervention.

Metabolic reprogramming and epigenetic remodeling are critical features of tumorigenesis. The process of metabolic reprogramming causes metabolites like Succinyl-CoA to accumulate. Succinylation, which depends on succinyl-CoA as the direct donor group, plays a crucial role in regulating cancer metabolism. This involves the transfer of the succinyl group to the lysine residues of substrate proteins resulting in the alteration of the conformation and function of the proteins, modulating several signaling pathways, many of them involved in metabolism. There is growing evidence that succinylation can alter the activity and stability of metabolic enzymes and reshape metabolic networks. Furthermore, it precisely regulates gene expression through the epigenetic modification mechanisms of the histones and non-histone proteins. Lysine succinylation is thus a crucial hub linking tumor metabolic reprogramming and epigenetic remodeling. This review systematically summarizes the dynamic regulatory mechanisms of lysine succinylation and its critical roles in tumor metabolic reprogramming and epigenetic regulation. In the end, we discuss the crosstalk between succinylation and other post-translational modifications (PTMs) as well as recent advances in cancer therapies targeting succinylation.

Extracellular matrix (ECM) remodeling is a hallmark of colorectal cancer progression, yet the transcriptional mechanisms coordinating collagen deposition and matrix metalloproteinase activation remain incompletely understood. We performed integrated computational analysis of 680 samples across normal mucosa, adenoma, and carcinoma stages to characterize discoidin domain receptor (DDR)-mediated transcriptional networks during tumorigenesis. Stage-stratified correlation analysis of fourteen pathway genes revealed profound divergence between DDR1 and DDR2; DDR1 correlations remained weak across all stages, while DDR2 correlations strengthened 2.59-fold from normal to carcinoma. DDR2-COL11A1 exhibited the most dramatic coupling intensification, increasing from R2=0.007 in normal tissue to R2=0.549 in carcinoma, accompanied by 1.99-fold COL11A1 upregulation. Remarkably, pathway activation occurred despite stable DDR2 expression, indicating enhanced transcriptional coupling efficiency rather than receptor upregulation as the primary mechanism. Deep neural network classification achieved 93.14% accuracy distinguishing disease stages, with SHAP analysis independently validating DDR2-COL11A1 as the most important gene interaction for cancer classification. These findings establish DDR2-specific transcriptional coupling as a functionally important mechanism in colorectal cancer progression and identify COL11A1 as a critical downstream target, suggesting novel therapeutic strategies targeting coupling efficiency rather than receptor abundance.