Neoadjuvant dual HER2 blockade with trastuzumab and pertuzumab plus chemotherapy represents the current standard-of-care for HER2-positive breast cancer. However, treatment responses remain heterogeneous, underscoring the lack of clinically practical tools for predicting treatment efficacy and informing personalized therapy. Here, we developed HER2-LADDER (Layered AI-based Dual-targeteD anti-HER2 Recommendation), a spatially interpretable and clinically accessible artificial intelligence framework that integrates clinicopathological and spatial topological features from routine hematoxylin and eosin (H&E) and HER2 immunohistochemistry (IHC) slides. Using these spatially derived features, HER2-LADDER accurately predicted response to neoadjuvant TCbHP/PCbHP, achieving AUCs of 0.944 in the model construction cohort (N = 276), 0.917 in the temporal validation cohort (N = 82), and 0.869 in the trial-based validation cohort (N = 85). On the basis of HER2-LADDER scores, patients were stratified into Low (highly responsive), Medium (responsive), and High (resistant) groups, identifying candidates for treatment de-escalation (THP or TCbH/PCbH), standard-of-care (TCbHP/PCbHP), or alternative regimens (e.g., next-generation anti-HER2 antibody-drug conjugates), respectively. Importantly, Xenium in situ profiling further revealed biological correlates underlying model predictions, including HER2-enriched tumor cell aggregation and neutrophil-helper T-cell interactions, thereby highlighting the mechanistic interpretability of the model. Collectively, HER2-LADDER unites digital pathology and high-resolution spatial profiling into a clinically accessible AI framework, offering a robust, transparent, and biologically grounded tool to tailor individualized HER2-targeted therapy optimization.

Prostate cancer (PCa) represents a major global health concern due to biological heterogeneity and the complexity of its underlying molecular pathways, which contribute to substantial morbidity and mortality. Ongoing research continues to elucidate distinct molecular mechanisms that may inform diagnostic and therapeutic strategies. Among these, the prostate-specific membrane antigen (PSMA) has emerged as a pivotal biomarker and therapeutic target in PCa. PSMA is indirectly modulated by androgen signalling through the androgen receptor (AR) pathway and has been observed to undergo transient upregulation following treatment with AR targeting agents, such as darolutamide, particularly in patients with castration-resistant PCa. This transient increase in PSMA expression-termed the 'PSMA flare phenomenon'-may enhance the sensitivity and accuracy of PSMA-based molecular imaging and disease staging.

Melanoma shows one of the highest response rates to immune checkpoint inhibitors (ICIs), yet nearly half of patients experience primary or acquired resistance. While immune contexture strongly influences therapeutic efficacy, tumor cell-intrinsic features are increasingly recognized as key regulators of antitumor immunity. In particular, intratumoral heterogeneity driven by melanoma cell plasticity underlies diverse immune escape mechanisms. How this plasticity shapes ICI outcomes in patients remains poorly defined.

Chronic inflammation is a well-established driver of colorectal cancer (CRC), with the resulting inflammatory microenvironment facilitating tumor initiation and progression. The integrin CD11b/CD18, a leukocyte-specific heterodimeric adhesion receptor, mediates critical immunoregulatory functions during inflammatory responses. However, the roles and mechanisms of CD11b/CD18 in colitis-associated colorectal cancer (CAC) remain unclear.

Calvarial multilobular tumor of bone (MLTB) in dogs is treated typically by craniectomy. However, long-term outcome data are lacking.

Acquired drug resistance is a major cause of failure in gastric cancer treatment. The protein tyrosine phosphatase receptor type E (PTPRE) plays an oncogenic role in certain tumours; however, its function in chemotherapy-resistant gastric cancer remains unclear. Therefore, we analysed PTPRE expression in gastric cancer using The Cancer Genome Atlas. In vitro experiments were then conducted to investigate the effects of PTPRE on the resistance of cancer cells to 5-fluorouracil (5-FU) and its potential mechanisms. The results were further validated in vitro using xenograft studies. We found that PTPRE is upregulated in gastric cancer tissues and participates in the induction of 5-FU resistance. Mechanistic studies revealed that PTPRE suppressed ferroptosis in gastric cancer cells and promoted 5-FU resistance by activating the Src/FAK pathway to upregulate TRIB3 expression. In summary, PTPRE suppresses ferroptosis in gastric cancer cells via the Src/FAK/TRIB3 signalling pathway, thereby inducing 5-FU resistance. Intervention with PTPRE and its downstream targets may represent a potential approach for the clinical treatment of 5-FU-resistant gastric cancer.

This study compared the efficacy of first-line alectinib versus ceritinib and evaluated the role of upfront brain radiotherapy (RT) in patients with ALK-positive non-small cell lung cancer (NSCLC) and brain metastases (BM).

Immune checkpoint inhibitors have revolutionised the management of non-small cell lung cancer (NSCLC) without oncogenic addictions and have improved its prognosis. A manifestation of acquired resistance to immunotherapy, which is typically seen in a restricted number of lesions and metastatic locations (oligoprogression), has been reported. In cases of oligoprogressive disease, local ablative therapies may represent the main therapeutic approaches, and their significance is further amplified for patients with metastatic NSCLC undergoing immunotherapy.

This study investigates the correlation between blood-brain barrier (BBB) damage and cognitive impairment in patients suffering from untreated lung cancer. The study aims to understand the impact of BBB permeability on cognitive function and brain structure in this patient population.

Endometrioid endometrial cancer (EEC) is the most prevalent gynecological malignancy. While early-stage EEC typically carries a favorable prognosis, late-stage EEC shows significantly poorer outcomes, with a five-year survival rate of only 17-19%. Co-occurring PTEN and CTNNB1 variants are frequent in EEC and linked to poor prognosis. To investigate their functional impact, we generated uterine-specific Pten knockout mice and dominantly stabilized Ctnnb1 mutant mice (Pgrcre/+Ptenf/fCtnnb1f(ex3)/+; Ptend/dCtnnb1f(ex3)/+). These double-mutant mice exhibited significantly reduced survival compared to single Pten knockout (Pgrcre/+Ptenf/f; Ptend/d) mice. Histopathology revealed aggressive, metastatic endometrioid cancer in Ptend/dCtnnb1f(ex3)/+ mice; these mice developed myometrial invasion by four weeks of age - unlike Ptend/d mice. Transcriptomic analysis identified activation of multiple oncogenic pathways, including WNT/CTNNB1, PI3K/AKT, basal cell carcinoma, sonic hedgehog signaling and epithelial-mesenchymal transition (EMT). Immunohistochemistry confirmed hallmark features of EMT in the uterus of double-mutant mice, including strong downregulation of E-cadherin (CDH1) and upregulation of the EMT regulator SNAIL (Snai1). These findings demonstrate that synergistic mutations of PTEN and CTNNB1 promote early invasion, EMT activation, and metastatic progression, offering mechanistic insight into the aggressive behavior and poor clinical outcomes associated with this subtype of EEC.

To investigate the predictive value of serum cytokines for treatment response to initial radioactive iodine therapy (RAI) in patients with intermediate- or high-risk differentiated thyroid cancer (DTC), and to develop a novel nomogram model for this purpose.

Colorectal cancer (CRC) is a pathology highly influenced by lifestyle and dietary habits, with ethanol consumption recognized as one of the most impactful and modifiable risk factors. Intestinal microbiota alterations have been observed both in high alcohol consumers and in the progression of intestinal polyps to CRC. The diet-microbiota-host interplay has a key role in health and disease. This perspective critically evaluates the mechanistic interplay within this triad and its potential role in mediating alcohol-induced toxicity, as well as its implications for the etiological link between alcohol consumption and CRC risk. Furthermore, we synthesize current advances and delineate key challenges for future research in this area. A particular focus is posed on the analysis of the anatomopathological, nutritional and microbiota data collected from individuals with intestinal polyps in a pilot study carried out in the region of Asturias, Northern Spain.

Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates that arise in non-lymphoid tissues under chronic inflammatory conditions and during tumor development. Although TLS have often been associated with a favorable prognosis and enhanced therapeutic responsiveness, their biological and clinical significance in breast cancer is highly heterogeneous and cannot be adequately captured by a simple TLS-positive versus TLS-negative classification. In this review, we summarize the structural organization and developmental stages of TLS, with an emphasis on the functional relevance of maturation, including germinal center formation. We further discuss current concepts regarding the mechanisms driving TLS initiation and maturation, including stromal activation, chemokine-guided immune cell recruitment, and high endothelial venule-mediated lymphocyte trafficking. In addition, we examine the major dimensions of TLS heterogeneity in breast cancer, including differences in maturity, spatial location, molecular subtype, and immune cellular composition, and discuss how these variables shape antitumor, immunoregulatory, and context-dependent TLS functions. We also evaluate the current approaches for TLS identification and classification, highlighting the strengths and limitations of histopathology, immunophenotyping, multiplex imaging, and transcriptomic inference. Finally, we discuss the prognostic and predictive relevance of TLS in breast cancer, the barriers limiting its clinical translation, and key priorities for future research. Overall, TLS status represents a promising but context-dependent biomarker and potential therapeutic intermediate whose interpretation requires standardized classification and a deeper mechanistic understanding.

Ovarian cancer, particularly high-grade serous ovarian cancer (HGSOC), exhibits a generally poor response to immune checkpoint inhibitors, and its underlying mechanisms remain incompletely defined. This observation suggests that an immunological framework focused predominantly on CD8+ cytotoxic T cells is insufficient to fully explain immune resistance in ovarian cancer. Increasing evidence highlights the importance of tertiary lymphoid structures (TLS) and follicular immune responses in coordinating antitumor immunity and shaping therapeutic outcomes.

Melanoma stem cells may contribute to tumor progression not only through intrinsic plasticity, but also by shaping the immune microenvironment. However, their interaction with the monocyte-macrophage compartment remains poorly understood.

Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine malignancy in which neural activity is implicated in tumor progression. Nevertheless, whether primary SCLC elicits systemic effects on the brain remains uncertain.

Gastric cancer is a leading cause of cancer-related mortality, with limited efficacy of immunotherapies due to intratumoral heterogeneity, an immunosuppressive microenvironment, and antigen-loss escape. The optimization of chimeric antigen receptor (CAR) T-cell therapy targeting PD-L1 and Claudin18.2 (CLDN18.2) is crucial for improving the antitumor response.

Cytokeratin-positive interstitial reticulum cell (CIRC) tumor, a subtype of fibroblastic reticular cell tumor (FRCT), is an extremely rare primary neoplasm of lymph nodes and soft tissue, with limited understanding of its clinicopathological and molecular features. This case is the first identification of human leukocyte antigen loss of heterozygosity (HLA LOH) in CIRC tumor, which provides novel insights into immune evasion mechanisms and potential therapeutic implications.

Colorectal carcinoma (CRC) is one of the most common malignant tumors worldwide, with treatment options including surgery, chemotherapy, radiotherapy, and targeted therapy. However, the overall efficacy of treatment for metastatic CRC (mCRC) remains unsatisfactory. In recent years, immune checkpoint inhibitors (ICIs) have shown good therapeutic effects in some patients, but the overall response rate remains low. Physical ablation (PA) is a localized treatment modality that, in addition to eradicating targeted lesions, promotes anti-tumor immunity by releasing tumor-associated antigens from damaged tumor cells. ICIs enhance this PA-elicited anti-tumor immune response by inhibiting immunosuppressive pathways and unleashing T-cell activity, resulting in a synergistic anti-tumor effect. This article reviews the latest research on the treatment of mCRC with PA (mainly including radiofrequency ablation, microwave ablation, and cryoablation) combined with ICIs, focusing on how PA combined with ICIs can reshape the tumor immune microenvironment to produce a synergistic anti-tumor immune response. Finally, this article also discusses the challenges currently faced by the combined treatment and looks forward to future research directions, aiming to provide a new treatment strategy to improve the clinical prognosis of mCRC.

This study developed a multifunctional MnFe2O4/TiVNbMoC3-cRGD (MXenes) nanocomposite for targeted photothermal- photodynamic therapy against bladder cancer.