Macrophages, as central players in the tumor microenvironment (TME), exhibit remarkable plasticity, shifting between pro-inflammatory M1 and immunosuppressive M2 states. This polarization directly influences the response to radiotherapy in cancers. While M1 macrophages promote antitumor immunity, M2 macrophages contribute to immune evasion, metastasis, and treatment resistance. Ionizing radiation, while designed to kill tumor cells, can inadvertently alter macrophage polarization within the TME. High-dose and particle-based radiotherapies tend to favor M1 polarization, enhancing tumor control, while conventional radiotherapy often induces M2 macrophages, promoting radioresistance. These shifts in macrophage phenotype are driven by changes in metabolic signaling, hypoxia, and cytokine production within the TME, which together dictate the outcome of therapy. Emerging strategies aim to manipulate macrophage polarization to overcome radiotherapy-induced resistance, including the use of immune checkpoint inhibitors, nanoparticles, and metabolic reprogramming agents. By targeting macrophage recruitment, survival, and reprogramming, these therapies can potentially improve the efficacy of radiotherapy and reduce tumor recurrence. Understanding and leveraging macrophage plasticity holds promise for optimizing cancer treatment and enhancing patient outcomes in the era of precision oncology.

Colorectal cancer (CRC) is shaped by inherited genetic susceptibility, metabolic reprogramming, epigenetic regulation, and tumor microenvironment (TME) heterogeneity. Lactylation has recently emerged as an epigenetic mechanism that links lactate accumulation to chromatin remodeling and transcriptional regulation. However, the roles of lactylation-related genes in CRC initiation and progression, particularly from the perspective of SNP-based germline genetic variation, remain to be elucidated.

Multiple myeloma (MM) is characterized by genomic instability and therapeutic resistance. Emerging evidence indicates that germline DNA damage response (DDR) mutations, including BRCA1/2, ATM, and CHEK2 variants, contribute to MM susceptibility, clonal evolution, and treatment response. Inherited DDR defects promote chromosomal instability, reshape the immune microenvironment, and facilitate therapy-driven disease progression. Recent advances in multiomics profiling, single-cell sequencing, and liquid biopsy have improved the functional interpretation and clinical monitoring of DDR alterations. Moreover, DDR-associated vulnerabilities provide opportunities for precision therapies, including PARP inhibitor-based synthetic lethality strategies. This review summarizes the mechanistic and clinical significance of germline DDR alterations in MM and highlights their translational potential in precision oncology.

ObjectiveTo investigate the association of preoperative hypoalbuminemia (serum albumin <35 g/L) with clinicopathological characteristics and survival outcomes in patients with gastric cancer undergoing radical gastrectomy and to construct a nomogram based on prognostically relevant clinicopathological variables.MethodsThis retrospective cohort study included patients with gastric cancer who underwent radical gastrectomy. Clinicopathological variables and survival outcomes were compared between groups. Univariate and multivariable analyses were performed to identify variables associated with prognosis, and a nomogram was constructed based on significant predictors.ResultsPreoperative hypoalbuminemia was significantly associated with adverse clinicopathological characteristics, including anemia, lymphocyte depletion, advanced American Joint Committee on Cancer stage, vascular invasion, and perineural invasion. Kaplan-Meier analysis showed that hypoalbuminemia was associated with poorer overall survival. In multivariable Cox regression analysis, lymph node metastasis remained independently associated with overall survival, whereas preoperative hypoalbuminemia was not an independent prognostic factor.ConclusionsPreoperative hypoalbuminemia may reflect unfavorable nutritional and inflammatory status and was associated with adverse clinicopathological characteristics and poorer survival in univariate analysis. However, it was not independently associated with overall survival after multivariable adjustment. Lymph node metastasis remained an independent prognostic factor.

This review systematically explores the dynamic regulatory roles of lysine lactylation (Kla) in the tumor microenvironment (TME) and its clinical translational potential. As an emerging post-translational modification, Kla modifies histones and non-histone proteins via lactate generated by the Warburg effect, thereby reshaping tumor metabolism and immune landscapes. Mechanistically, Kla orchestrates metabolic reprogramming and immunosuppression through key signaling pathways such as HIF-1α, mTOR, and NF-κB. Specifically, it promotes the activation of immunosuppressive cells while inhibiting cytotoxic CD8+ T cells and NK cells, fostering tumor immune escape. Preclinical studies demonstrate that targeting lactate metabolism or lactylation enzymes restores immune effector functions and enhances immune checkpoint therapy efficacy. However, challenges such as tumor heterogeneity, metabolic plasticity, and systemic toxicity remain. Future research should focus on Kla's crosstalk with other epigenetic modifications, spatiotemporal dynamics in TIME, and clinical translation to unlock its potential as a biomarker and precision oncology target.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Inflammatory responses and lipid metabolism disorders are known to influence cancer development; however, their combined effects on HCC progression remain unclear. This study examined the associations between lipid profiles and inflammatory markers with HCC stage.

Durvalumab maintenance following concurrent chemoradiotherapy (CCRT) is the standard treatment for unresectable stage III non-small cell lung cancer (NSCLC); however, some patients discontinue treatment before completing 12 months. We explored whether pretreatment peripheral blood inflammatory and nutritional markers are associated with durvalumab non-completion.

Microwave ablation induces heating of tissue. High energy results in thermal cell death, but low energy treatment without tissue necrosis has been shown to induce cutaneous immunity in an HPV wart model. It is approved as an effective cancer treatment for solid organ cancers, and therefore it is of interest to know if microwave delivered directly to the skin holds potential for treatment of skin cancer. This pilot study focused on transcriptomic profiling of cutaneous melanoma metastases to investigate molecular changes associated with microwave therapy. Seven adult patients with skin metastases from malignant cutaneous melanoma, not resolving on standard treatment, were recruited. Microwave energy was applied to separate melanoma metastases. Morphological, histological, and transcriptomic changes assessed via tissue RNA sequencing were evaluated. Three participants showed complete response, while four showed partial response by histological assessment. In complete responders, skin lesion RNA sequencing after treatment, compared with baseline, identified increased inflammation (CXCL5, CXCL8, IL1A, COL1A1) and downregulated cancer markers (PRAME, S100B, MLANA, STK32A). Compared with partial responders, complete responders showed enrichment of FABP4 and reduced expression of cancer markers. Microwave therapy produced local tumor responses and associated inflammatory transcriptomic changes in complete responders, supporting further clinical evaluation in cutaneous melanoma metastases.

To evaluate the comparative prognostic utility of next-generation flow cytometry (NGF) and dual-tracer PET/CT in measuring minimal residual disease (MRD), this prospective real-world study enrolled 118 newly diagnosed multiple myeloma (NDMM) patients. Patients underwent post-treatment assessment using NGF (sensitivity 10-5) and dual-tracer PET/CT using 11C-acetate (AC-PET) and 18F-FDG. While AC-PET showed a numerically higher detection rate compared to FDG-PET in paired analyses (n = 45), a significant discordance was observed between imaging and immunophenotypic assessment. NGF detected MRD in 38.2% of paired cases compared to 11.8% by AC-PET; however, AC-PET uniquely identified metabolic activity in extramedullary sites for two NGF-negative patients, highlighting the value of functional imaging in resolving spatial heterogeneity. In the landmark survival analysis (n = 104), NGF positivity was identified as a robust independent predictor for inferior progression-free survival (HR 2.21, 95% CI 1.01-4.81; p = 0.046) and overall survival (HR 4.97, 95% CI 1.23-20.01; p = 0.026), transcending baseline risk stratifications. Furthermore, longitudinal monitoring revealed that patients achieving sustained MRD negativity experienced significantly superior outcomes compared to those with transient negativity or persistent disease. These findings establish NGF as the standard prognostic biomarker for MM, while AC-PET serves as a critical complementary tool for detecting extramedullary escape, supporting a risk-adapted MRD strategy that integrates molecular depth with metabolic imaging.

Interleukin-6 (IL-6) signalling is a key driver of breast cancer progression, activating pro-survival, pro-inflammatory and metastatic programs through its receptors, IL-6R and GP130. Elevated IL-6 levels correlate with poor prognosis in breast cancer patients and persistent IL-6/STAT3 activation promotes tumour proliferation, metastasis, angiogenesis and therapy resistance. Although therapeutics targeting this pathway have shown promise, most have focused on individual signalling nodes and yielded limited efficacy in breast tumours. In this study, we generated murine monoclonal antibodies targeting ectodomains of IL-6R and GP130 receptors involved in IL-6/IL-6R/GP130 complex formation and humanized the lead candidates E17 (anti-IL-6R) and NA7 (anti-GP130). The resulting humanized antibodies, huE17 and huNA7, exhibited target specificity and effectively inhibited IL-6 induced STAT3 activation and tumour promoting phenotypes in vitro. In vivo evaluation using orthotopic breast cancer xenografts and agarose plug angiogenesis assays showed both individual and combined antibody treatments significantly suppressing tumour growth. Structural modelling suggested that huE17 and huNA7 engage receptor surfaces spanning multiple ectodomains of IL-6R and GP130, consistent with disruption of IL-6/IL-6R/GP130 complex receptor assembly. Together, these findings support the preclinical development of huE17 and huNA7 and the potential of dual IL-6R and GP130 targeting in IL-6-driven breast cancer.

Giant retroperitoneal tumors are rare and pose significant surgical challenges due to delayed presentation, massive size, and complex anatomical relationships. Although these tumors encompass biologically heterogeneous entities, many share common surgical features that complicate operative management, particularly in cases with predominant spindle cell histology.

Chemoresistance remains a major barrier in treating oral squamous cell carcinoma (OSCC). This study investigated whether the marine-derived sesterterpenoid heteronemin (HET) suppresses chemoresistant OSCC (SAS-CR) cells and elucidated its underlying mechanisms. HET dose- and time-dependently reduced SAS-CR viability, inhibited clonogenic growth, and exhibited stronger cytotoxicity than cisplatin or 5-fluorouracil. Furthermore, HET induced S-phase arrest by downregulating proliferation and cell-cycle proteins (PCNA, c-Myc, cyclin A, cyclin D3, CDK4, and CDK6). Concurrently, it triggered intrinsic apoptosis, characterized by mitochondrial depolarization, upregulated cleaved caspase-3/PARP and Bax, and downregulated Bcl-2. This caspase-dependent apoptosis was partially reversed by pan-caspase inhibitor Z-VAD-FMK. Transcriptomic profiling linked these phenotypes to metabolic stress, revealing alterations in the tricarboxylic acid cycle, mitochondrial respiration, and copper homeostasis. Consistently, HET elevated intracellular Cu2+ levels and reduced FDX1, SDHB, and lipoylated DLST/DLAT protein expression-cytotoxic effects that were attenuated by the copper chelator tetrathiomolybdate (TTM). Additionally, HET increased reactive oxygen species (ROS) production, whereas ROS scavenger N-acetylcysteine (NAC) attenuated HET-induced apoptosis and restored cuproptosis-related markers. In a zebrafish model, HET demonstrated negligible toxicity while reducing tumor-associated fluorescence and FDX1 expression. Collectively, HET effectively suppresses chemoresistant OSCC through coordinated ROS-dependent apoptosis and cuproptosis-associated mitochondrial stress, supporting its development as a therapeutic candidate for refractory OSCC.

Data on GH and prolactin (PRL) co-secreting pituitary neuroendocrine tumors (GH/PRL-PitNETs), a subtype of acromegaly, remain limited. In particular, comparative analyses of clinical outcomes, including remission rates, between GH/PRL-PitNETs and GH-secreting pituitary neuroendocrine tumors (GH-PitNETs) are scarce.

Treatment with NovaSure® endometrial ablation is approved for patients with heavy menstrual bleeding (HMB) without evidence of malignant or premalignant lesions. This analysis addresses the rare but clinically relevant situation in which endometrial carcinoma (EC) or atypical hyperplasia (AEH) is identified histologically after endometrial ablation in premenopausal patients.

Lung cancer remains the leading cause of cancer-related mortality worldwide, non-small cell lung cancer (NSCLC) is a major histological subtype. Lactylation, a newly discovered post-translational modification, and its impact on lung cancer are still poorly understood. In this study, using immunohistochemical staining and immunofluorescence staining analyses, we found elevated levels of pan-lactyl proteins and histone H3 lysine 18 lactylation (H3K18la) in tumor tissues. Subsequently, siLDHA and siLDHB treatment or Nala treatment were respectively adopted as H3K18la deletion or acquisition functional models to demonstrate the effects of H3K18la on the proliferation, migration and apoptosis phenotypes of NSCLC cells. Through chromatin immunoprecipitation sequencing (ChIP-seq) analysis and ChIP-qPCR experiments, we demonstrate for the first time that lactylation of H3K18 regulates the transcriptional activity of the Transcobalamin 1 (TCN1) promoter. High expression of TCN1 in lung cancer is associated with poor patient prognosis. Functional experiments in vitro and in vivo revealed that knockdown of TCN1 suppressed the malignant progression of NSCLC. Finally, mechanistic investigations uncovered that TCN1 activates the PI3K/AKT signaling pathway. These results reveal a novel mechanism by which H3K18la precisely regulates the promoter activity of specific genes and enhance our understanding of the specific roles of lactate and lactylation in modulating tumor biology. Targeting H3K18la and TCN1 may represent potential therapeutic strategies for NSCLC.

Tyrosine kinase inhibitors (TKIs) have improved outcomes in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) and are increasingly incorporated into treatment protocols of Philadelphia chromosome-like (Ph-like, ABL-class) ALL. However, central nervous system (CNS) relapse remains a significant challenge. Imatinib, a first-generation TKI, demonstrates limited CNS penetration in adults, yet data in children are sparse.

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.