Abstract Background Epstein–Barr virus (EBV)–associated gastric cancer (EBVaGC) is distinct molecular subtype of gastric cancer for which effective preventive and targeted therapeutic strategies remain limited. This study aimed to design and evaluate multiepitope vaccine candidates targeting four EBV proteins critically involved in this disease, namely BZLF1, EBNA1, LMP1, and LMP2. Methods An integrated immunoinformatics and reverse vaccinology approach was employed to predict and screen MHC-I (CTL), MHC-II (HTL), and B-cell epitopes. Selected epitopes were assembled into multiepitope vaccine constructs, which were then evaluated for physicochemical properties, potential interactions with immune receptors, and post-injection immune responses using computational simulations. Results A total of 20 immunodominant epitopes in each CTL, HTL and LBL were identified and selected based on their predicted antigenicity, immunogenicity, non-allergenicity, and non-toxicity, while the selected MHC-II epitopes were additionally predicted to induce IFN-γ, IL-2, IL-4, and IL-10 responses. Global population coverage analysis estimated worldwide coverage of 98.74%. The final vaccine construct comprised 1,091 amino acids and exhibited favorable physicochemical properties with acceptable structural quality, as indicated by a ProSA Z-score of − 2.28 and 79.1% of residues located in the most favored regions of the Ramachandran plot. Disulfide engineering identified six residue pairs with the potential to enhance structural stability. Molecular docking demonstrated favorable binding of the vaccine construct to TLR9, with a HADDOCK score of − 165.4 ± 0.7 kcal/mol. Molecular dynamics simulations further supported the structural feasibility of the vaccine–TLR9 complex, yielding an average RMSD of 1.253 nm; 963.3 hydrogen bonds, and SASA of 911.3 nm². Meanwhile, normal mode analysis corroborated the dynamic stability of the complex. Codon optimization in the pET-28a(+) vector resulted an optimal codon adaptation index (CAI = 1.0) and GC content of 57.86%, suggesting high potential for recombinant expression in Escherichia coli . Immune simulations further predicted coordinated humoral and cellular immune responses, accompanied by immunological memory formation following simulated vaccination regimen. Conclusion The study proposed multiepitope vaccine candidate targeting crucial antigen of EBVaGC based immunoinformatics-based approach. The construct predicted to have favorable in silico immunological and structural properties. However, further experimental validation is required to confirm its safety and immunogenic potential.
Liver cancer, mainly hepatocellular carcinoma (HCC), remains a global health burden marked by poor prognosis with limited therapeutic efficacy, and high recurrence rates. HCC remains one of the most lethal malignancies worldwide, with limited therapeutic options and high resistance to conventional treatments. Despite low therapeutic efficacy, molecular heterogeneity, treatment resistance and high recurrence rate, hepatocellular carcinoma (HCC) is still a significant health problem worldwide. These restrictions have stimulated the research of focused methods for delivering therapeutic genetic payload into cancer cells. Bacteriophages have been gaining growing attention as an emerging delivery platform due to their genetic versatility, ease of engineering, ability to be surface modified and payload targeted. In this narrative review, the therapeutic potential of engineered bacteriophages in the context of HCC therapy is critically analyzed focusing on phage display-mediated tumor targeting, phage-mediated intracellular gene delivery, TRAIL gene delivery, and CRISPR/Cas-based therapeutic strategies. It has been previously noted in the literature that phage display can be used to attach tumor-targeting ligands to the surface of a phage, which may aid in the recognition of receptors at the tumor site and promote targeted delivery to the receptor. Therapeutic application is stunted by inefficient trafficking to the cytosol, endosomal degradation, immune recognition and clearance, vector stability, manufacturing scalability and regulatory issues. In conclusion, engineered bacteriophages are a promising and versatile tool for targeted gene delivery in HCC but more mechanistic, preclinical and translational research is needed to prove their therapeutic effectiveness and clinical usefulness for this purpose.
Abstract Background Colorectal carcinoma is among the most prevalent malignancies worldwide. PD-L1 is an immune-checkpoint ligand that can contribute to tumor immune evasion whereas BCL2 is an anti-apoptotic protein involved in cell-survival pathways, with its mutation frequently observed in various human cancers. This study aimed to evaluate the prognostic significance of immunohistochemically identified PD-L1 and BCL2 proteins in colorectal carcinoma. Materials Sixty paraffin-embedded colorectal carcinoma tissue specimens were subjected to immunohistochemistry (IHC) staining for PD-L1 and BCL2 expression, which was analyzed using the DAKO scoring system (0: 0–4%, 1: 5–24%, 2: 25–49%, 3: 50–74%, 4: 75–100%). Result PD-L1 protein expression was detected in all patients, with immunoreactivity noted in 33.3% (score 3), 31.7% (score 2), 20.0% (score 4), and 15.0% (score 1), with score 0 cases showing no detectable immunoreactivity Similarly, Bcl-2 protein expression was identified in all colorectal carcinoma patients, with immunoreactivity observed in 38.3% (score 3), 25.0% (score 2), 20.0% (score 4), and 16.7% (score 1), while no detectable immunoreactivity was seen in score 0 cases. Conclusions These findings highlight the ubiquitous expression of PD-L1 and Bcl-2 in colorectal carcinoma and their potential role as prognostic biomarkers, providing insights into their relevance in cancer progression and therapeutic response.
Abstract Background Acute leukemia is the most common cancer in children, highlighting the importance of early diagnosis. RECAF is an AFP receptor that is abnormally re-expressed in various malignant tumors, serving as a promising biomarker for tumors. Aim This study aimed to assess the clinical utility of RECAF expression by flow cytometry immunophenotyping in pediatric de novo acute leukemia patients. Methods Our study was conducted in 80 pediatric patients with acute leukemia, comprising 40 newly diagnosed ALL patients, 40 newly diagnosed AML patients, and 40 age- and sex-matched non-malignant control subjects. Flow cytometric analysis for the Acute Leukemia panel and RECAF expression was performed on all subjects, along with other laboratory and clinical parameters. Results Our study revealed that RECAF expression was significantly higher in patients with acute leukemia than in controls. We also established a cutoff of ≥ 13.31% for positive RECAF expression by flow cytometry to distinguish RECAF-positive acute leukemia patients from FECAF-negative patients and normal controls. Conclusion Our findings suggest that RECAF could be an important biomarker for differentiating leukemic blasts and may become a useful tool for monitoring measurable residual disease in the future. Such advancements have the potential to improve clinical outcomes and enhance patient monitoring and management for this high-risk group.
Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the absence of estrogen, progesterone, and HER2 receptors, limiting effective targeted therapies. Increasing evidence suggests that metabolic reprogramming, a hallmark of TNBC progression, is driven by underlying epigenetic mechanisms such as DNA methylation. The represented study performed an integrative analysis of transcriptomic (RNA-seq) and methylome data to uncover the metabolic–epigenetic interplay in TNBC. Differential gene expression analysis using DESeq2 revealed significant dysregulation of key metabolic genes, including upregulation of genes encoding glycolytic and serine biosynthesis enzymes and downregulation of metabolic tumor suppressors. Genome-wide methylation profiling identified extensive cytosine–phosphate–guanine (CpG) hypermethylation events associated with transcriptional repression, particularly in promoter regions. Integrative analysis pinpointed a subset of metabolism-related genes exhibiting both differential expression and methylation, such as FBP1 , RASSF1A , and PHGDH . Pathway enrichment analysis highlighted aberrations in glycolysis/gluconeogenesis, fatty acid metabolism, and one-carbon pathways (adjusted p < 0.01). Importantly, TNBC patients with hypermethylated metabolic gene signatures displayed significantly shorter overall survival (log-rank p < 0.05). These findings reveal that DNA methylation-driven metabolic dysregulation contributes to TNBC aggressiveness and may provide novel biomarkers and therapeutic targets at the metabolic–epigenetic interface.
Abstract Background Sentinel lymph node biopsy (SLNB) is standard for axillary staging in early breast cancer. While the combination of radioisotope and blue dye (e.g., patent blue V, PBV) remains the standard, it has limitations including logistics, variable identification rate (IR), and allergic potential. Indocyanine green (ICG) fluorescence is a promising alternative, but high-quality comparative evidence is needed. Methods This was a single-center, prospective, randomized controlled trial. Forty patients with early-stage, node-negative breast cancer were allocated to SLNB using either ICG ( n = 20) or PBV ( n = 20). All patients subsequently underwent completion level I–II axillary lymph node dissection (ALND) as the pathological reference standard for diagnostic performance assessment. Primary outcome was sentinel lymph node (SLN) IR. Secondary outcomes included detection time, number of SLNs retrieved, false-negative rate (FNR), and safety. Results Baseline characteristics were comparable between groups. The SLN IR was significantly higher with ICG (100% [20/20]) than with PBV (75% [15/20], p = 0.047). ICG was associated with a significantly shorter median detection time (14.5 vs. 24.0 min, p < 0.001) and retrieved more SLNs (mean: 3.6 vs. 2.4, p = 0.002). Most critically, ICG demonstrated 100% sensitivity, specificity, negative predictive value (NPV), and overall diagnostic accuracy, with a 0% FNR. In contrast, PBV achieved a sensitivity of 75%, an overall diagnostic accuracy of 90%, and an FNR of 25%. No ICG-related adverse events occurred. PBV caused skin discoloration in 75% of patients and one (5%) allergic reaction. Conclusion ICG fluorescence achieved a higher SLN IR, shorter detection time, higher sensitivity, lower FNR, and fewer tracer-related adverse events than PBV as a single tracer for SLNB in patients with early-stage breast cancer. These findings suggest that ICG is a promising standalone tracer when radioisotope mapping is unavailable. Larger multicenter studies are required before widespread adoption can be recommended.
Machine learning (ML) is transforming cancer research and care by enabling analysis of complex, high-dimensional datasets spanning genomics, transcriptomics, proteomics, imaging, and clinical records. By improving risk stratification, accelerating detection and diagnosis, and supporting treatment selection, ML has the potential to enhance survival outcomes while increasing efficiency across oncology workflows. This review synthesizes key developments in ML for oncology, covering foundational algorithms alongside emerging approaches. We highlight major application areas including early cancer detection, tumor classification, molecular subtyping, biomarker discovery, prognosis estimation, multi-omics integration, computational pathology, pharmacogenomics, and clinical decision support. We also summarize commonly used datasets, discuss the importance of interpretability for clinical trust, and outline barriers to translation such as data heterogeneity, bias, and regulatory constraints. Finally, we describe future directions, including federated learning, graph neural networks, longitudinal modeling, and integration of real-world and wearable data to support precision oncology. This review is intended for cancer researchers, clinicians, and data scientists seeking a practical overview of ML methods, opportunities, and translational considerations in oncology.
Mediastinal sampling is essential for diagnosing and staging thoracic diseases, particularly non-small cell lung cancer (NSCLC). Traditional mediastinoscopy has been the gold standard; however, Endobronchial Ultrasound-guided Transbronchial Needle Aspiration (EBUS-TBNA) has emerged as a minimally invasive alternative. This systematic review compares the economic evaluations of EBUS-TBNA to determine their cost-effectiveness, healthcare resource use, and overall economic impact. A systematic review was conducted following PRISMA guidelines. Databases searched included PubMed and ScienceDirect, using keywords such as “EBUS-TBNA,” “mediastinoscopy,” and “cost-effectiveness.” Inclusion criteria focused on studies evaluating studies comparing EBUS-TBNA with traditional mediastinoscopy, with direct economic comparisons between EBUS-TBNA and traditional mediastinoscopy. Articles published in English within the last 10–15 years were included, covering randomized controlled trials, cohort studies, and economic modeling analyses. Four studies met the eligibility criteria after screening and full-text review. The review revealed that EBUS-TBNA consistently demonstrated lower costs and better cost-effectiveness compared to TMC. In the study by Steinfort et al. [1], EBUS-TBNA reduced costs by AU5,898 per patient compared to mediastinoscopy. Similarly, Chouaid et al. [2] reported cost savings of €1,450 per patient in France. EBUS-TBNA avoided mediastinoscopy in 80
Oral squamous cell carcinoma (OSCC) arises in the context of diverse etiological exposures, such as tobacco, alcohol, areca nut use and viral infections. This etiological heterogeneity drives distinct molecular alterations, contributing to tumor complexity and significant challenges in identifying robust, clinically applicable biomarkers. To resolve this, we employed an integrative bioinformatics approach, analyzing five gene expression datasets retrieved from the GEO repository, which encompass heterogenous clinical samples with diverse clinical stages of OSCC Differentially expressed genes (DEGs) were identified using stringent thresholds (|LogFC|≥ 1.5 to 3.0; p < 0.05), followed by GO and KEGG pathway enrichment analysis. A protein–protein interaction (PPI) connectome was generated, leading to identification of key hub genes using five topological properties. The biological relevance of hub genes was validated via GEPIA, HPA, immune infiltration analysis, and miRNet. Screening of datasets provided 1764 DEGs. Enrichment analysis revealed dysregulation in immune response, metabolic processes, remodeling of the extracellular matrix, and inflammatory signaling. Five hub genes, EGFR, FN1, IL6, STAT1, and PTPRC, emerged as central regulators with distinct expression-survival profiles and associations with immune infiltration patterns. Notably, STAT1 and IL6 demonstrated context-dependent behavior, reflecting both tumor-intrinsic and microenvironment-derived expression patterns. This study highlights five key genes with potential diagnostic, prognostic, and therapeutic relevance in OSCC, emphasizing their consistency across clinically heterogeneous patient cohorts. These results extend a mechanistic understanding of OSCC pathobiology, thus promising leads towards the development of clinically robust biomarkers.
Hepatocellular carcinoma (HCC) is a malignancy with high global incidence and mortality, whose significant heterogeneity and poor prognosis pose severe clinical challenges. While artificial intelligence (AI) shows potential in HCC imaging, pathology, and prognosis, its "black-box" nature limits clinical adoption. Explainable AI (XAI) aims to reveal the decision-making logic of AI models. This narrative review synthesizes recent advances of XAI across four key domains of HCC research. In imaging diagnosis, techniques such as Grad-CAM and SHAP have enabled semantic alignment between AI outputs and clinical standards like LI-RADS, enhancing interpretability. In biomarker discovery, XAI has progressed from identifying single markers to revealing functional gene modules and molecular subtypes through multi-omics integration. In treatment efficacy prediction, XAI-based models have quantified feature contributions to therapeutic responses, supporting individualized treatment stratification. In prognosis assessment, XAI has enabled dynamic risk stratification by integrating clinical, imaging, and pathological features. However, three cross-cutting limitations persist across these domains: explanations remain predominantly correlational rather than causal, a semantic gap exists between pixel-level heatmaps and high-level clinical reasoning, and most models are static, unable to adapt to evolving clinical data. Current research is moving toward causal inference frameworks, concept-driven interpretability, and interactive, dynamic systems. In summary, XAI is transitioning from a retrospective explanation tool toward a prospective clinical decision partner, yet bridging the gap between explanation and actionable decision support remains the central challenge.
Abstract Background Recently, uterine transposition has been proposed as a novel technique for fertility preservation in young females undergoing radiation therapy for pelvic malignancies. Patients and methods This is an interventional pilot study including six female patients with pelvic malignancies planned to receive pelvic radiation aiming at preserving their fertility after a multidisciplinary team decision to have uterine transposition. Our study aims to assess the feasibility of this novel technique. Results Six patients underwent uterine transposition. Three of them were done through open technique, with successful repositioning. The other three patients underwent laparoscopic uterine transposition, one of them underwent repositioning and still receiving chemotherapy for Ewing’s sarcoma, the other two patients are still receiving radiation therapy after transposition. Unfortunately, one of them died of disease and adjuvant therapy complications four months after laparoscopic uterine transposition. Conclusion Uterine transposition is a feasible procedure with safe outcomes. The preliminary results carry a promising hope for better fertility preservation in young patients undergoing radiation for pelvic malignancies.
Abstract Background The chances of oral squamous cell carcinoma (OSCC) being diagnosed at an early stage are very low, and this leads to a poor prognosis. The presence of circulating miRNAs (miRNAs) in blood or saliva is now a potential non-invasive diagnostic biomarker, although the diagnostic accuracy of the studies reported remains vastly different due to differences in biofluids, miRNA panels, disease spectrum, and platforms. Methods We did a meta-analysis of diagnostic accuracy and a systematic review in accordance with PRISMA-DTA 2020 guidelines (PROSPERO: CRD420251274288). Articles that evaluated circulating miRNAs in any biofluid in diagnosing OSCC were taken into consideration. A Bayesian bivariate random-effects model was used to pool together the sensitivity, specificity, likelihood ratios, diagnostic odds ratios and the summary receiver operating characteristic (sROC) curves. Heterogeneity sources were analyzed using pre-constructed subgroup analysis and meta-regression. Results The number of studies that were evaluated in totality was seventeen and seven were incorporated in the meta-analysis. The pooled sensitivity of the circulating miRNAs towards the detection of OSCC was 0.89 (95% CI: 0.77–0.95) and the pooled specificity was 0.88 (95% CI: 0.75–0.95) . It had a pooled positive likelihood ratio (PLR) of 7.25 (95% CI: 3.42–16.08) , a negative likelihood ratio (NLR) of 0.13 (95% CI: 0.05–0.27) , and a diagnostic odds ratio (DOR) of 59.69 (95% CI: 14.33-209.95) . Good performance in discriminating was also noted in the sROC curve with an area under the curve value of approximately 0.90. However, substantial between-study heterogeneity was observed (τ ≈ 0.93 for sensitivity; τ ≈ 0.83 for specificity), and the 95% credible intervals around the DOR were wide (14.33–209.95). Individual studies of multi-miRNA panels reported AUCs up to 0.98, though pooled subgroup estimates were limited by small study numbers and wide uncertainty. Conclusions Circulating miRNAs and in particular multi-miRNA saliva-based profiles provide promising but heterogenous diagnostic accuracy for OSCC. While individual panel studies have reported high AUCs, the current pooled evidence—derived from only seven small, mostly case-control studies of advanced-stage disease—does not yet establish utility for true early detection or population screening.
Abstract Objective This study aimed to systematically synthesize and separately quantify the pooled safety profiles of bispecific antibodies (BsAbs) targeting PD-1/CTLA-4 or PD-1/VEGF in patients with non-small cell lung cancer (NSCLC), and to descriptively summarize class-specific safety patterns. Methods Following PRISMA guidelines, we systematically reviewed prospective clinical trials published through January 2026. A total of 17 studies, encompassing 1802 patients, were included. Single-arm proportion meta-analyses were conducted separately for each BsAb class using random-effects models. No formal between-class statistical comparison was performed. Given the clinical heterogeneity across included cohorts, including differences in study phase, treatment line, molecular subtype, and treatment regimen, pooled estimates were interpreted descriptively. Subgroup analyses by treatment regimen, treatment line, and individual BsAb agent were considered exploratory. Because of the limited number of cohorts within each phase stratum, the impact of study phase was assessed descriptively rather than through formal stratified meta-analysis. Results In separate pooled analyses, the incidence of grade 3 or higher treatment-related adverse events (TRAEs) was 41.79% for PD-1/CTLA-4 BsAbs and 43.51% for PD-1/VEGF BsAbs. Exploratory subgroup analyses suggested different patterns of heterogeneity across the available cohorts. In PD-1/CTLA-4 BsAb studies, AE rates appeared to vary across individual agents, whereas in PD-1/VEGF BsAb studies, higher AE rates were observed mainly in chemotherapy-containing regimens. These observations should be interpreted cautiously because they may reflect differences in the distribution of included agents, patient populations, study phases, and treatment strategies rather than inherent class-specific toxicity mechanisms. Regarding tolerability, the pooled treatment discontinuation rate due to TRAEs was 10.26% in the PD-1/CTLA-4 analysis and 4.44% in the PD-1/VEGF analysis. The pooled incidence of immune-related adverse events (irAEs) was 46.68% in the PD-1/CTLA-4 analysis and 27.10% in the PD-1/VEGF analysis, whereas the pooled rates of grade 3 or higher irAEs were low in both analyses. Conclusion This systematic review provides a descriptive synthesis of available safety data for PD-1/CTLA-4 and PD-1/VEGF BsAbs in NSCLC. Because the included cohorts differed substantially in study phase, treatment line, molecular background, and concomitant therapies, the pooled AE estimates should not be interpreted as direct comparative evidence. Instead, the findings should be viewed as hypothesis-generating signals that require validation in more homogeneous prospective studies or head-to-head trials.
Abstract Objective Lymph nodes (LNs) in medical images often have fuzzy boundaries, vary in size and shape, and have intensities similar to those of neighboring tissues, making accurate segmentation challenging. To address this issue, we propose a multi-scale attention-enhanced network (MSA U-Net) that integrates channel-wise and spatial attention mechanisms for automatic segmentation of metastatic pelvic LNs associated with uterine malignancies from sagittal magnetic resonance imaging (MRI). Methods This network integrates a U-Net backbone, fuses features from different encoder levels at skip connections, and feeds the fused features into the decoder at each layer. Different receptive fields are used at the bottleneck nodes to capture multiscale contextual information. A detection head is added to the bottom layer of the network and the detection results are used to assist in the final segmentation of the image. A lightweight design of the convolutional block attention module is also implemented to optimize feature representation. Results The experimental results demonstrate that the proposed network achieves better segmentation performance compared to the baseline model. The proposed network achieves a mean intersection over union of 0.76, an average pixel accuracy of 0.97, a precision of 0.78, a recall of 0.97, a Dice coefficient of 0.82, and a Hausdorff distance of 2.21. Conclusions The proposed MSA U-Net segmentation network effectively segments LNs in uterine MRI images, outperforming existing segmentation methods. This study provides a reliable and automated method to help clinicians detect LN, thus improving clinical decision-making.
Abstract Invasive lobular carcinoma (ILC) can metastasize to the gastrointestinal tract and closely mimic primary gastric adenocarcinoma, especially when signet-ring cell morphology is present. Here, we report the case of a 65-year-old woman who presented with epigastric discomfort and abdominal fullness. Esophagogastroduodenoscopy showed multiple skipped mucosal lesions in the stomach, and an endoscopic biopsy revealed poorly differentiated adenocarcinoma with signet-ring cell features. She was initially diagnosed as having primary gastric cancer, with imaging showing multiple bone metastases. Later, a newly detected breast lump was diagnosed as ILC on core needle biopsy, which was positive for estrogen receptor (ER) and progesterone receptor, but negative for HER2. As no signet-ring cells were found, the initial assumption was double primary cancers of the stomach and breast. Accordingly, the multidisciplinary team discussion concluded that the breast lump represented a second primary, early-stage breast cancer, making lumpectomy and sentinel lymph node biopsy appropriate to achieve local control and prevent progression-related complications. Subsequent lumpectomy revealed ILC with signet-ring cell morphology, prompting re-evaluation of the gastric biopsy with extended immunohistochemistry, which confirmed metastatic breast origin (ER+, GATA3+, HNF4α–). Therefore, the diagnosis was revised to stage IV ILC with gastric and bone metastases. This case highlights the diagnostic challenges posed by ILC with gastric metastases exhibiting signet-ring cell morphology, and emphasizes the importance of integrating clinical history with careful, parallel pathological and immunohistochemical evaluations.
Abstract Purpose Sarcomas are rare, aggressive and unpredictable tumors that arise from mesenchymal tissues. Despite treatment, outcomes for advanced or metastatic cases remain poor. Anlotinib is a new oral tyrosine kinase inhibitor that blocks multiple angiogenic pathways and has shown encouraging results in solid tumors. This review aims to summarize and clarify the current evidence on anlotinib’s role in treating sarcoma. Methods A systematic search across five major databases up to February 2025 identified clinical studies that evaluate anlotinib in sarcoma patients. Eligible studies included randomized controlled trials and observational studies evaluating anlotinib in advanced or metastatic sarcoma. Pooled estimates for median progression-free survival (mPFS) and overall survival (mOS) were calculated using random-effects models. Results Twenty-one studies involving 1,230 patients were included. The pooled mPFS was 6.7 months and the mOS was 19.3 months. Results varied widely due to differences in sarcoma subtype, disease stage, and prior therapies, yet most studies showed meaningful tumor control and manageable toxicity. Conclusions Anlotinib appears to be a promising therapy for refractory or metastatic sarcomas. It offers modest yet real improvements in survival and quality of life. Larger, multicenter and biomarker-guided studies are needed to define which patients benefit most and how this drug can be best integrated into future treatment strategies.
Gastric cancer is a highly prevalent malignancy of the digestive tract in China. Conventional chemotherapeutic drugs and human epidermal growth factor receptor 2 (HER2)‑targeted agents such as trastuzumab remain limited by significant challenges in the treatment of GC, including high rates of drug resistance, significant toxicity and adverse effects, and suboptimal tolerability. The advent of antibody-drug conjugates (ADCs) has marked a paradigm shift in the therapeutic landscape. This review systematically summarises the structural design, mechanisms of action, and current clinical applications of ADCs in HER2-positive or HER2-low advanced gastric cancer. The present review focuses on key clinical trial data for new-generation ADCs, specifically trastuzumab deruxtecan (T-DXd) and disitamab vedotin (RC48), drawing from the DESTINY-Gastric series and the RC48-C008 study. The review systematically synthesised data on efficacy, safety profiles, resistance mechanisms, and future therapeutic directions. New-generation ADCs have demonstrated significant improvements in objective response rates (ORR) and overall survival (OS) compared with traditional chemotherapy in later-line treatment settings. Emerging evidence also suggests the presence of activity in HER2-low-expressing populations. A systematic assessment of adverse drug reactions highlights both common events (e.g. gastrointestinal reactions, haematologic toxicity) and distinctive adverse events (e.g. interstitial lung disease), with corresponding management strategies. A comprehensive analysis of multiple resistance mechanisms, including HER2 heterogeneity, endocytic barriers, drug efflux, and target mutations, is conducted. The present study demonstrates that ADCs represent a transformative therapeutic modality for HER2-positive or HER2-low cases. Ongoing advancements in ADC structural optimisation, combination strategies with immune checkpoint inhibitors show great promise in terms of further improving clinical outcomes. The objective of this review is to furnish clinicians and researchers with a detailed reference for future clinical practice and investigation.
Abstract Background Delivering devastating news of cancer is a universal challenge, but cultural and religious contexts impact disclosure. In Saudi Arabia, family engagement frequently influences communication, yet little is known about stakeholders’ perspectives on gynecological cancer. Methods This mixed-methods study used validated questionnaires and semi-structured interviews. Results A total of 737 participants were included (54.1% public, 18.5% physicians, 16.0% relatives, and 11.4% patients); the majority were female (67.8%) and Saudi citizens (81.9%), with a median age of 38 years. Results Overall, 90.5% of participants preferred that a cancer diagnosis be disclosed to the patient rather than withheld. However, only 25–36% supported disclosing a bad prognosis, with physicians being the least supportive (6.7%, p < 0.0001). Most groups supported the use of the term “chemotherapy” (88–98%). 94% of clinicians favored disclosing treatment failure, but only 61% of patients and 53% of the public agreed ( p < 0.0001). More than half of patients (51.5%) and three-quarters of clinicians (73.1%) were opposed to concealing diagnoses at the request of the family. Patients greatly preferred engagement in treatment (66.3%) and end-of-life talks (80.7%), whereas physicians showed less support. In terms of communication dynamics, most patients preferred that the head of the medical team disclose directly to them, face-to-face, and framed with “Allah’s will.” Conclusions Although patients, family, the public, and clinicians mostly supported direct disclosure, there were still disagreements over prognosis and end-of-life talks. These findings emphasize the importance of culturally sensitive, ethically based communication training to enhance patient-centered treatment in gynecological oncology.
Thymic epithelial tumors, including thymoma and thymic carcinoma, are rare malignancies for which platinum-based chemotherapy is the standard first-line treatment. Second-line options include chemotherapy, targeted therapy, immune checkpoint inhibitors (ICIs), or combination regimens. While thymoma has been strongly associated with paraneoplastic autoimmune disorders, previous clinical trials have demonstrated an increased risk of severe immune-related adverse events, such as myocarditis when treating thymoma patients with ICIs. Herein, we report a case of recurrent B3 thymoma in a patient who developed myocarditis, overlapping Guillain–Barré syndrome, and myasthenia gravis exacerbation after receiving a single dose of 100 mg pembrolizumab therapy. The patient recovered after steroid pulse therapy, intravenous immunoglobulin administration, and plasma exchange.
Background: Recurrent/metastatic head and neck squamous cell carcinoma (R/M-HNSCC) carries a poor prognosis despite the current standard of care. This study aimed to investigate the efficacy and safety of a novel non-cisplatin-containing chemo-immunotherapy regimen combining a programmed cell death protein 1 (PD-1) inhibitor and a taxane, in platinum-ineligible or platinum-refractory R/M-HNSCC patients. Materials and Methods: This retrospective analysis of medical charts included 24 patients aged ≥18 with unresectable R/M-HNSCC, eastern cooperative oncology group performance status ≤2, no prior immune checkpoint inhibitor (ICI) therapy, and adequate follow-up. All patients received a PD-1 inhibitor and a taxane. The primary endpoints were progression-free survival (PFS) and objective response rate (ORR), and the secondary endpoints were overall survival (OS) and toxicity. Results: The ORR was 50%, the disease control rate was 66.7%, the median PFS was 6.4 months, and the median OS was 11.6 months. The average time to response was 3.3 months, with a median duration of response of 5.0 months. Common adverse events included anemia (58.3%), hypothyroidism (29.2%), and dermatitis (25%). Grade ≥ 3 adverse events occurred in 20.8% (5/24) of the patients, with one ICI discontinuation due to severe dermatitis; others were manageable. Conclusion: The results of this real-world retrospective analysis showed satisfactory efficacy including ORR, PFS, and OS, and manageable toxicity for PD-1 inhibitor/taxane combination therapy as first-or later-line treatment in ICI-naïve R/M-HNSCC patients. Larger prospective studies are warranted.
