Enzalutamide resistance in advanced prostate cancer often leads to treatment-induced neuroendocrine prostate cancer (t-NEPC), characterized by aggressive lineage plasticity. The molecular regulators governing neuroendocrine differentiation and phenotypic transition are not well understood. Here, we characterize the functional role of the transmembrane protein TMEM59L in driving PCa progression, lineage plasticity and therapeutic resistance.

We combined bulk RNA sequencing, single-cell RNA sequencing, and spatial transcriptomics datasets to assess TMEM59L expression patterns and their association with clinical features. We investigated the biological functions of TMEM59L using enzalutamide-resistant (EnzR) PCa cell lines in vitro and corresponding mouse xenograft models in vivo. Mechanistic interactions were elucidated through molecular assays, including co-immunoprecipitation (Co-IP), GST pull-down and molecular docking.

TMEM59L expression is negatively regulated by androgen receptor (AR) signalling and markedly elevated in EnzR PCa tissues. In PCa cells, ectopic TMEM59L expression induced a neuroendocrine-like phenotype, enhanced stemness, promoted epithelial-mesenchymal transition (EMT) and conferred enzalutamide resistance. Conversely, TMEM59L depletion restored drug sensitivity and significantly suppressed EnzR tumour growth in vivo. Mechanistically, TMEM59L directly interacts with MUC1 to facilitate its nuclear accumulation, thereby activating the downstream β-catenin/MYC signalling axis. Importantly, pharmacological inhibition or genetic silencing of MUC1 effectively reversed TMEM59L-induced neuroendocrine differentiation, stemness and enzalutamide resistance.

Our findings uncover a previously unrecognized TMEM59L/MUC1/β-catenin/MYC signalling cascade associated with neuroendocrine differentiation and enzalutamide resistance in PCa. Targeting this regulatory axis presents a promising therapeutic strategy to circumvent resistance to next-generation AR signalling inhibitors.

Artificial intelligence (AI)-based computer-aided detection (AI-CADe) systems can improve adenoma detection during colonoscopy. However, successful clinical implementation depends on diagnostic performance and user acceptance, usability, and workflow integration. This study evaluated user perceptions before and after the clinical implementation of AI-CADe.

This single-center, repeated, cross-sectional descriptive survey evaluated the endoscopy unit staff perceptions of AI-CADe at the National Cancer Center. Two anonymous online surveys were administered before and 1 month after the system installation. The surveys assessed the perceived diagnostic benefits, workflow impact, user satisfaction, concerns regarding false-positive detection, dependence on AI, and factors influencing acceptance and continued use. The analyses were descriptive and exploratory.

Twenty-nine and 25 participants completed the pre- and post-installation surveys, respectively. Positive responses regarding the interest in AI-CADe, perceived adenoma detection rate improvement, expected lesion removal, patient satisfaction, procedural satisfaction, and workflow impact were reported in both survey phases. Concerns regarding overdetection, unnecessary biopsies, and increased dependence on AI were also reported. Accuracy and sensitivity were the most frequently selected adoption factors, followed by cost and false-positive rates. Open-ended feedback included positive comments regarding lesion recognition, procedural support, and limitations related to repeated alerts, false-positive alarms, delayed detection, and system responsiveness.

Endoscopy unit staff members showed favorable perceptions of AI-CADe and recognized its potential value in colonoscopy practice. However, concerns regarding false-positive detection, workflow integration, and dependence on AI indicate the need for user-centered optimization and long-term real-world evaluation.

Androgen receptor (AR) activation alters chromatin structure in prostate cancer (PC) cells, but its impact in nonmalignant prostate epithelial cells (NPEC) remains poorly characterized due to lack of representative models. We leveraged our previously established NPEC (RWPE-1-AR and RWPE-1-Ctrl) and PC (LNCaP-pcDNA3.1 and LNCaP-ARhi) cell models to profile androgen-driven chromatin responses using assay for transposase-accessible chromatin with sequencing (ATAC-seq). In the absence of androgen, NPEC and PC cells exhibited widespread differences in chromatin accessibility. Androgen stimulation amplified these differences, revealing distinct AR-mediated chromatin remodeling between the cell types. Androgen-sensitive regions were enriched for nuclear receptor binding sites (AR and glucocorticoid receptor), with AP-1 motifs more prominent in NPEC and FOXA1 motifs in PC cells. Comparison with ATAC-seq profiles obtained from clinical samples showed that NPECs resembled benign prostate hyperplasia, while PC cells mirrored untreated and castration-resistant PC, supporting the relevance of our models. Integration of ATAC-seq and mRNA-sequencing (mRNA-seq) identified model-specific AR target genes, including CDKN1C/p57 in NPEC, which may contribute to the previously observed androgen-induced growth arrest in these cells. These findings demonstrate that AR activation reprograms chromatin accessibility in normal prostate epithelium, revealing fundamental regulatory differences compared to the tumor context and underscore the importance of physiologically relevant cell models.

Vascular endothelial growth factor receptor-2 (VEGFR-2) is a vital mediator of angiogenesis. Therefore, VEGFR-2 inhibition is considered a promising therapeutic target to combat cancer. In the present study, a series of 22 imidazo[4,5-b]pyridine-acrylonitrile-based derivatives was designed and synthesized. All compounds were evaluated for their VEGFR-2 inhibitory activity. Seven of the tested compounds showed high inhibitory activity against VEGFR-2 with IC₅₀ (0.029-0.087 µM) compared to reference drug sorafenib IC₅₀ = 0.091 µM. Four of these derivatives were selected for in vitro cytotoxic activity against breast cancer (MCF-7) and hepatocellular (HepG2) carcinoma cell lines, showing IC₅₀ (0.073-0.196 µM) and (0.20-0.21 µM), respectively, relative to sorafenib IC₅₀ 0.16 and 0.19 µM, respectively. Compound 2f exhibiting a superior VEGFR-2 inhibition (IC₅₀ = 0.029 µM compared to sorafenib IC₅₀ = 0.091 µM) and cytotoxicity against MCF-7 and HepG2 (IC₅₀ = 0.073 µM and IC₅₀ = 0.09 µM, respectively), was subjected to cell cycle analysis, apoptosis assay, and molecular modeling studies, which strongly supported the results. It caused cell cycle arrest at G2/M phase by 13.67% and a promising apoptosis induction. 2f exhibited a promising binding score and pose inside the VEGFR-2 active sites. It also showed a good safety profile with a moderate selectivity index. Based on the prediction of physicochemical and pharmacokinetic properties for 2f, it showed excellent prediction results to be orally bioavailable.

Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigm for patients with gynecologic malignancies. ICIs have led to improved survival outcomes in uterine and cervical cancer, although with only modest success in ovarian cancer. In endometrial cancer, The Cancer Genome Atlas provided the framework for the molecular classification of endometrial cancer, enabling identification of the predominant predictive biomarker: mismatch repair (MMR) status. US Food and Drug Administration approvals for ICI monotherapy and in combination with targeted therapy based on MMR status quickly followed. Further research demonstrated a role for ICIs in combination with chemotherapy regardless of MMR status in the initial treatment of advanced or metastatic disease. In cervical cancer, ICIs are approved for use in combination with chemotherapy-sensitized radiation and in combination with systemic chemotherapy in patients who have recurrent or metastatic disease. In ovarian cancer, the tumor microenvironment, low tumor mutational burden, and the absence of a reliable predictive biomarker have limited the efficacy of ICIs, with most combination approaches failing to demonstrate meaningful benefit. A notable exception is KEYNOTE-B96, a randomized trial of pembrolizumab versus placebo with weekly paclitaxel, with or without bevacizumab, in patients with platinum-resistant ovarian cancer. Continued investigation into predictive biomarkers, resistance mechanisms, and alternative therapeutic targets is critically needed to extend the benefits of immunotherapy to patients with ovarian cancer. In this review, the authors describe the current immunotherapy landscape across gynecologic cancers, highlighting when ICI use is, and is not, supported by the evidence.

Odontogenic myxoma (OM) is an uncommon, locally aggressive odontogenic neoplasm with characteristic histologic and clinico-radiographic features but with potential for histologic overlap with other odontogenic and non-odontogenic entities and a non-specific immunoprofile. Widespread loss of heterozygosity (LOH) has been recently described in rare cases of OM. The aim of this study was to determine whether widespread LOH represents a recurrent molecular signature that can be leveraged for clinical decision-making. Allele-specific copy number variation data from chromosomal microarray were generated from 7 OM, comprising a combined prospective and retrospective cohort. Four tumors arose in the mandible and 3 in the maxilla in patients ranging in age from 18 to 94 years (median: 44), with tumor size ranging from 2.2 to 13.0 cm. Variable amounts of fibrous stroma (odontogenic "fibromyxoma") were present in 4/7 OM, and hypercellularity not typically appreciated in conventional OM was present in 3/7 cases. All OM (7/7) demonstrated widespread LOH, with 5 cases showing a near-haploid/low hypodiploid genomes (multiple monosomies) and 2 cases showing evidence of pseudo-hyperdiploidy due to probable endoreduplication. Both pseudo-hyperdiploid cases were ≥10 cm in size; 1 represented local recurrence. Chromosomes 1 to 3, 6, 9, 11, 13, 15, and 22 demonstrated LOH in ≥75% of cases (chromosomes 1 to 3, 6, and 9 in 100% of cases), while chromosomes 5, 12, 19, and 20 universally retained heterozygosity. Altogether, widespread LOH is a recurrent event in OM and a novel finding in odontogenic pathology, and allele-specific copy number variation analysis can serve as a diagnostic adjunct in challenging cases.

Patients and their partners coping with hematologic malignancies (HMs) experience significant psychological and relational challenges. Dyadic coping (DC) plays a critical role in couples' adaptation under cancer treatments.

To synthesize existing evidence on DC strategies, influencing factors, and outcomes among couples facing HMs.

Guided by the JBI framework, this review systematically searched for and included original studies of any design that examined DC in adult couples where one partner had hematologic cancer. Data on study design, population characteristics, coping strategies, factors, and outcomes were extracted and summarized narratively.

Nine articles across 8 studies were reviewed. Commonly used DC strategies included stress communication, protective buffering, and common coping. Some evidence suggested the potential usefulness of couple-based programs that incorporate communal coping training, but overall, no studies directly examined factors influencing DC. Studies using the Actor-Partner Interdependence Model revealed reciprocal associations between partners' coping and well-being. Negative strategies were consistently associated with higher distress, poorer relationship satisfaction, and greater unmet needs. Positive strategies showed mixed effects, generally associated with improved relationship satisfaction and quality of life, though sometimes related to increased distress or unmet needs.

DC significantly affects relationship quality, psychological well-being, and quality of life in HM couples. Positive strategies can foster mutual support but may also increase strain, whereas negative strategies exacerbate distress.

Findings highlight the clinical importance of supporting couples as relational units. Oncology nurses should integrate tailored, couple-based interventions that address both shared and individual coping needs.

Postoperative circulating tumor DNA (ctDNA) is a strong marker of molecular residual disease after curative-intent colorectal cancer resection, but prognostic validity alone does not establish treatment-decision utility. We performed a PRISMA 2020 systematic review and meta-analysis with search coverage through March 31, 2026, separating randomized ctDNA-guided treatment-decision evidence from prospective prognostic cohorts, platform-trial evidence, implementation evidence, and ongoing trials. Thirty-eight reports or programs were included in the evidence map, and seven independent prospective cohorts contributed to the prognostic meta-analysis. Postoperative ctDNA positivity was associated with increased recurrence risk (pooled hazard ratio, 7.60; 95% CI, 4.70-12.31), with substantial heterogeneity (I²=80.6%) and a wide prediction interval (1.60-36.25). Decision evidence was scenario-specific: DYNAMIC supports consideration of selective stage II colon cancer de-escalation, whereas DYNAMIC-III did not establish non-inferiority for routine stage III de-escalation. Current evidence does not support routine empiric escalation for MRD-positive disease. Postoperative ctDNA should therefore be interpreted as a powerful risk-stratification tool whose treatment-changing role remains limited to selected clinical contexts.

Kirsten rat sarcoma viral oncogene homolog (KRAS)^G12D is the most prevalent RAS mutation in solid tumors, associated with poor prognosis, and occurs mainly in pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). Here we evaluated GFH375, a compound that targets both 'ON' (GTP-bound) and 'OFF' (GDP-bound) states of KRAS^G12D proteins, in a phase 1 dose-escalation trial in patients with advanced solid tumors harboring the KRAS^G12D mutation. The primary endpoints were safety/tolerability, the maximum tolerated dose and recommended phase 2 dose. The secondary endpoints included pharmacokinetics, objective response rate (ORR), duration of response, disease control rate, time to response, progression-free survival (PFS) and overall survival (OS). A total of 74 heavily treated patients with KRAS^G12D-mutant advanced solid tumors were administered orally with GFH375 once or twice daily, including 43 patients with PDAC, 16 with NSCLC and 10 with CRC. Overall, GFH375 was well tolerated and no dose-limiting toxicity was observed among the 22 patients in the dose-escalation part; the maximum tolerated dose was not reached. The recommended phase 2 dose of GFH375 was declared as 600 mg once daily. One (1.4%) grade 5 treatment-related adverse event was reported as septic shock. Grade ≥3 treatment-related adverse events occurred in 36.5% (27/74) of the patients and were more prevalent in patients previously treated with immune checkpoint inhibitors. In patients with PDAC, the confirmed ORR was 35.1% (13/37), with a median duration of response of 5.6 months; the median PFS and median OS were 5.5 months and 9.9 months, respectively. In patients with NSCLC, the confirmed ORR was 35.7% (5/14); the median PFS and median OS were 5.5 months and 13.4 months, respectively. This trial demonstrated the manageable safety/tolerability and encouraging antitumor activity of GFH375 monotherapy. The phase 2 portion of this trial with expansion cohorts for NSCLC, PDAC, CRC and other solid tumors is ongoing. ClinicalTrials.gov identifier: NCT06500676 .

Prostate cancer is a major contributor to cancer-related mortality in men, and enzalutamide is a primary treatment option for advanced prostate cancer. Polyamines are ubiquitous amine molecules involved in tumorigenesis, cancer development, and drug resistance. This study aims to explore how spermidine/ spermine N1-acetyltransferase 1 (SAT1)-mediated polyamine metabolism influences prostate cancer progression and enzalutamide sensitivity. Through comprehensive bioinformatics screening, SAT1 was identified as a key regulator negatively associated with spermine abundance in prostate cancer. Analyses of clinical samples showed that increased SAT1 expression was positively linked to higher Gleason scores and more nodal metastases. Functional assays confirmed that knocking down SAT1 suppressed cancer cell proliferation, migration, invasion, and enzalutamide resistance, whereas overexpressing SAT1 enhanced these phenotypes. By promoting spermine catabolism, SAT1 triggered the activation of the JAK1/STAT3 pathway. Xenograft mouse models revealed that SAT1 knockdown inhibited tumor growth and improved the response to enzalutamide via the spermine-JAK1/STAT3 signaling axis. Notably, STAT3 gene was a transcriptional regulator of SAT1. These findings uncover a novel mechanism by which SAT1 facilitates tumor progression and decreases enzalutamide sensitivity, highlighting its potential as a therapeutic target for prostate cancer.