Circulating long non-coding RNAs (lncRNAs) are emerging as minimally invasive biomarkers for cancer detection; however, their clinical utility remains insufficiently validated. We evaluated the diagnostic performance of plasma lncRNAs and developed and externally validated multivariable models for detecting non-metastatic colon cancer.

Plasma lncRNA expression was quantified using reverse transcription quantitative PCR (RT-qPCR) in a training cohort of patients with histopathologically confirmed non-metastatic colon cancer and healthy controls. Multivariable logistic regression models integrating molecular and demographic variables were developed in the training cohort and externally validated in an independent cohort.

Nine candidate lncRNAs were evaluated, of which five (CCAT2, HOTAIR, LINC00909, PVT1, and UCA1) were consistently detectable in plasma and significantly upregulated in patients with colon cancer. A multivariable model combining UCA1, HOTAIR, and PVT1 with age and sex achieved an area under the ROC curve (AUC) of 0.97 in the training cohort and of 0.87 in the validation cohort. Internal bootstrap validation showed limited optimism (optimism-corrected AUC, 0.95), and calibration analysis demonstrated good agreement between predicted and observed probabilities. At a sensitivity-oriented threshold, the model reached 90% sensitivity and 69% specificity. A simplified model based on UCA1 retained good discrimination but with reduced overall performance.

Plasma lncRNA-based multivariable models show promise as minimally invasive tools for the early detection of colon cancer and highlight the importance of external validation in biomarker development.

The 6th edition of the World Health Organization Classification of Soft Tissue and Bone Tumors (STB6) integrates the latest scientific and molecular discoveries with decades of pathological expertise to establish a globally accepted common language for diagnosis and clinical behavior. In this volume, the "essential" and "desirable" diagnostic criteria have been refined, considering different resource settings, ensuring accuracy while maintaining flexibility. A tumor type (entity) is a tumor in which multiple parameters (eg, clinical, histopathological, and/or genetic features) differ from those of other tumor types. In total, 19 new entities met these criteria and were added. A subtype is different in at least one dimension from the main tumor type (clinical, histopathological, or genetic), preferably resulting in a different treatment or outcome. A morphological pattern (no longer "variant") is important for pathologists to be aware of to facilitate recognition but is not associated with different clinical behavior. The classification was drafted by 203 editors and authors from 27 countries, representing genetics, medical oncology, surgical oncology, orthopedic surgery, and radiology, in addition to pathology. STB6 includes soft tissue tumors (n=116), bone tumors (n=46), vascular tumors of soft tissue and bone (n=18), undifferentiated spindle and round cell sarcomas (n=4), hematopoietic and dendritic cell neoplasms (n=6), and genetic syndromes (n=6). In total, 62 sarcomas are included. A consensus was reached among the expert editorial board. In this review, we highlight changes in tumor classification in STB6, including recently described tumor types, novel diagnostic markers, recent discoveries in molecular genetics, and improvements in prognostication.

Endoscopic biopsy is fundamental for diagnosing gastrointestinal lesions, yet the effectiveness of AI assistance on endoscopists' biopsy strategies and efficiency for detecting gastric neoplasms remains unclear. This study aims to investigate this effectiveness.

This study is a secondary analysis of a randomized controlled trial (AI group: n = 13,440; control: n = 12,561) compared AI-assisted versus standard screening. The AI system marked high-risk and low-risk lesions with red and blue boxes, respectively. The AI group was stratified into red-box and non-red-box subgroups. Outcomes included neoplasm biopsy efficiency and proportion of non-biopsied documented lesions. The patient-level correlation between false-positive alerts and biopsy counts was examined. All analyses were based on the pathological results after centralized pathology review.

The non-biopsy rate was significantly lower in the red-box group than in the non-red box group and the control group (18.00% vs. 43.26%, 18.00% vs. 45.60%, both p < 0.001), suggesting that lesions were biopsied more frequently in the red-box group. Neoplasm biopsy efficiency was higher in the red-box group (8.19% vs. 0.36%, 8.19% vs. 1.77%, both p < 0.001). In negative binomial regression, red-box classification remained associated with a lower non-biopsy rate (IRR 0.393, 95% CI 0.360-0.429, p < 0.001). False-positive alerts showed a weak inverse correlation with biopsy counts (ρ = -0.182, p < 0.001).

Red-box classification was associated with more targeted biopsy sampling, while false-positive prompts were not associated with indiscriminate biopsies.

To evaluate the cost-effectiveness of darolutamide plus androgen deprivation therapy (DARO+ADT) versus enzalutamide plus ADT (ENZA+ADT) and apalutamide plus ADT (APA+ADT) as first-line androgen receptor pathway inhibitor (ARPI) double therapies for metastatic castration-sensitive prostate cancer (mCSPC) from a US healthcare sector perspective.

A partitioned survival model with three health states (progression-free mCSPC, progressed mCRPC, and death) projected lifetime costs and outcomes over a 30-year horizon with monthly cycles. DARO+ADT efficacy was derived from the ARANOTE trial; comparative efficacy for ENZA+ADT and APA+ADT was estimated via network meta-analysis-derived hazard ratios. Costs (drug acquisition, adverse event management, subsequent therapy, end-of-life care) and utilities were derived from trial data, published literature, and US cost sources. Costs and outcomes were discounted at 3% annually. Deterministic, probabilistic, and two-way sensitivity analyses assessed parameter uncertainty at a willingness-to-pay threshold of $150,000/QALY.

DARO+ADT generated 4.18 QALYs versus 4.03 (ENZA+ADT) and 3.99 (APA+ADT), driven by longer treatment persistence and lower adverse-event-related disutility. Versus ENZA+ADT, DARO+ADT yielded 0.15 incremental QALYs at $12,564 incremental cost (ICER: $85,108/QALY; net monetary benefit: $9,579). Versus APA+ADT, DARO+ADT was dominant (0.19 additional QALYs, $4,293 lower cost; net monetary benefit: $33,153). Two-way sensitivity analyses varying off-treatment utilities and post-discontinuation therapy costs showed that DARO+ADT remained cost-effective versus ENZA+ADT and dominant versus APA+ADT, respectively, across the parameter ranges tested. Probabilistic sensitivity analysis showed DARO+ADT was cost-effective in 51% and 52% of simulations versus ENZA+ADT and APA+ADT, respectively, which demonstrates uncertainty around the incremental findings.

The analysis relies on indirect comparisons and extrapolated modeling, factors that may limit the generalizability of the findings.

DARO+ADT was cost-effective versus ENZA+ADT and dominant versus APA+ADT, driven by improved tolerability and treatment persistence, supporting its value as a first-line mCSPC option.

The epidermal growth factor receptor (EGFR) is a validated therapeutic target for EGFR-mutant non-small cell lung cancer (NSCLC) and colorectal cancer, yet secondary T790M/C797S mutations and mesenchymal-epithelial transition factor (MET) amplification confer profound resistance to first-, second-, and third-generation EGFR tyrosine kinase inhibitors (TKIs). Indole hybrids integrate indole cores (including azaindoles and fused indoles) with diverse pharmacophores to achieve multi-site binding within the EGFR ATP pocket, conferring higher selectivity toward mutant EGFR than mono-indole scaffolds. This review systematically summarizes indole-based EGFR hybrids reported from 2021 to date into three categories: Phase I/II clinical candidates (1, 10), C797S-resistant preclinical leads (11a, 14a, 34, 48a, and 50a), and structurally diversified analogs with favorable blood-brain barrier (BBB) permeability and low systemic toxicity. Optimized indole hybrids exhibit prominent advantages over commercial TKIs, including enhanced binding affinity toward mutant EGFR, optimized pharmacokinetic profiles, minimized off-target effects, and the capacity to suppress compensatory oncogenic signals. We comprehensively dissect their binding modes, structure-activity relationships (SARs), in vitro/in vivo anticancer activities, and pharmacological features, and summarize critical substituent optimization rules for overcoming resistance. This work establishes a systematic structural basis for rational development of next-generation indole EGFR inhibitors against refractory EGFR-driven malignancies.

Surgical intervention and chemotherapy have enhanced the survival rates of patients with advanced gastric cancer. However, the development of chemotherapy resistance remains a major obstacle to effective treatment, leading to poor prognosis in these patients. Increasing evidence suggests that metabolic alterations play crucial roles in mediating chemoresistance. Here we investigate the effects of methylmalonic acid (MMA), a mitochondrial-derived metabolite, on GC progression and oxaliplatin resistance. Analysis of clinical samples revealed that elevated serum MMA levels correlated with chemoresistance and advanced tumor stage in GC patients. Functional assays identified that MMA promoted GC cell proliferation, migration, and resistance to oxaliplatin by attenuating DNA damage. Mechanistically, MMA suppressed oxaliplatin-induced γH2AX expression while upregulating ATAD5 and activating the ATM/ATR-mediated homologous recombination (HR) repair pathway. In vivo studies further confirmed that MMA impaired the antitumor efficacy of oxaliplatin, while silencing PCCA, a key enzyme in MMA synthesis, or supplementing vitamin B12, a regulator of MMA metabolism, reversed MMA-induced chemoresistance. These findings highlight MMA as a potential indicator for oxaliplatin resistance and a therapeutic target in GC. Therefore, targeting MMA through vitamin B12 supplementation could serve as a promising therapeutic strategy to overcome chemoresistance in GC patients with elevated MMA levels.

Immune checkpoint inhibitors (ICIs) are increasingly incorporated into perioperative cancer treatment, raising challenges in distinguishing immune-related adverse events (irAEs) from postoperative complications. We report a case of postoperative immune-related colitis following head and neck reconstructive surgery in a patient receiving long-term nivolumab. A man receiving nivolumab for gastric cancer, who was maintained on prednisolone for prior immune-related myositis, underwent subtotal glossectomy for advanced tongue cancer. Despite perioperative steroid coverage, he developed grade 3 diarrhoea on postoperative day 4. After infectious causes were excluded and CT revealed diffuse colitis, empirical corticosteroid therapy was initiated, with rapid symptom resolution; colonoscopy and biopsy supported a diagnosis of immune-related colitis. This case illustrates that irAE colitis should remain in the differential diagnosis of postoperative diarrhoea in patients with prior ICI exposure. As perioperative use of ICIs expands, clinicians should maintain a high index of suspicion for irAEs in patients presenting with postoperative diarrhoea.

Adamantinoma-like Ewing sarcoma (ALES) is an exceedingly rare neoplasm, typically arising in the head and neck. We present a case of bladder tumour initially diagnosed as urothelial carcinoma on transurethral resection, which after neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin and cisplatin and subsequent radical cystoprostatectomy was reclassified as ALES with no residual urothelial carcinoma.

Immunoglobulin heavy chain (IGH) enhancer translocations drive multiple myeloma (MM), but routine diagnostics resolve only 32 to 38% of cases. Here, we introduce TransFinder, a multiomic pipeline integrating SMRT long-read sequencing (LRS), Hi-C, H3K27ac ChIP-seq/CUT&Tag, and RNA-seq to systematically resolve cryptic translocations and their hijacked oncogenes by deconvoluting enhancer-promoter neo-loops at rearrangement breakpoints. Applied to MM, TransFinder identified that t(16;22)(q23;q11), a canonical translocation known to activate MAF, also hijacks enhancers to activate RAB36. It further uncovered previously unrecognized t(5;8)(q35;q24) and t(1;22)(q25;q13), which activate MYC and CBX7, respectively, through chromatin topology rewiring. CRISPR-Cas9-engineered t(1;22)(q25;q13) recapitulated CBX7 induction, and pharmacological inhibition of CBX7 suppressed myeloma cell proliferation. Beyond MM, TransFinder identified enhancer hijacking in chronic myeloid leukemia, where t(9;22)(q34;q11) repositioned an enhancer to activate BCR-ABL1, and pancreatic ductal adenocarcinoma, where t(2;12)(p24;q24) hijacked an enhancer to activate SDC1. Linking 3D genome architecture to oncogene activation, TransFinder decodes oncogenic structural variants and their trans-activities, establishing clinically actionable dependencies of noncoding drivers in malignancies.

Tumor metabolic programs shape immune evasion; however, the mechanism by which nutrient-transport systems rewire tumor-immune cell interactions remains unknown. We integrated bulk multi-omics, single-cell transcriptomics, spatial profiling, and functional assays for colorectal cancer-associated zinc-driven immunosuppressive circuit identification. Multi-omics analysis of 258 patients revealed three solute carrier transporter-centered archetypes, with an SLC39-enriched subtype aligned with consensus molecular subtype 2-like immune-desert tumors. SLC39-mediated zinc influx activated CDX2, which engaged a distal enhancer to induce tumor cell-specific CD24 expression. CD24⁺ tumor cells formed spatial niches with SIGLEC10-expressing monocyte-derived macrophages, dendritic cells, and resident macrophages, activating pleiotropic programs that suppress phagocytosis and remodel adhesion. SLC39 overexpression increased intracellular zinc and CD24 levels and reduced macrophage-mediated engulfment, whereas CD24 blockade restored phagocytosis. The zinc-CDX2-CD24-SIGLEC10 axis defined a terminal cancer cell state associated with poor survival and immune checkpoint blockade resistance. A seven-gene signature predicted immunotherapy responses across five colorectal cancer cohorts, identifying SLC39-driven zinc influx as a metabolic checkpoint governing immune exclusion.