Gastric cancer (GC) remains a major clinical challenge, with most patients exhibiting primary resistance to anti-programmed cell death protein-1 (anti-PD-1) immunotherapy and a lack of effective predictive biomarkers. Most advanced GC presents as immune-excluded "cold" tumors that respond poorly to immune checkpoint blockade. Traditional Chinese medicine (TCM) "Yong (abscess)" syndrome and the "treating GC as Yong" theory are widely applied in clinical practice, yet lack clear molecular and immunological mechanisms. Here, by translating these clinical observations into modern biological terms, we present an original, testable hypothesis proposing the "Yong" syndrome-cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) axis as the central molecular bridge connecting TCM syndrome subtypes, GC histological subtypes, and TME reprogramming. We hypothesize that heat-clearing and blood-activating TCM monomers activate cGAS-STING in a subtype-selective manner to convert "cold" tumors to "hot" immunogenic phenotypes, directly addressing the critical clinical dilemmas of primary anti-PD-1 resistance and insufficient biomarkers in GC immunotherapy. This hypothesis translates universal cGAS-STING mechanisms into a clinically actionable, syndrome-based precision strategy for GC.

Combining immune checkpoint inhibitors (ICIs) with chemotherapy has become a major clinical research focus. Patients with extensive-stage small-cell lung cancer (ES-SCLC) have been treated with different first-line ICI combinations in randomized controlled trials (RCTs), but the optimal combination strategy has not yet been determined. Our aim was to evaluate this strategy through a systematic review and meta-analysis.

Tumor immune barriers (TIBs) are spatially organized stromal-immune niches that restrict lymphocyte entry. To explain persistent immune-checkpoint blockade (ICB) resistance in clear cell renal cell carcinoma (ccRCC), we mapped TIBs and defined a peritumoral variant built from POSTN+ cancer-associated fibroblasts (CAFs) interlaced with APOE+ tumor-associated macrophages (TAMs). This niche excluded CD8+ T cells from tumor cores, and was enriched in poor-prognosis, ICB-refractory patients. Spatial transcriptomics and single-cell profiling showed TIB regions enriched for extracellular-matrix remodeling, immunosuppressive ligand-receptor circuits, and metabolic reprogramming. Mechanistically, tumor-derived TGF-β1 activated CAFs via SMAD signaling, inducing POSTN and recruiting APOE+TAMs through integrin and chemokine axes. TAMs secreted TGF-β1 and VEGFA, amplifying stromal programs and sustaining exclusion. Blocking POSTN reprogrammed macrophages, reduced matrix-mediated suppression, and restored CD8+ infiltration. In vivo, POSTN inhibition combined with ICB boosted antitumor immunity, reduced tumor burden, and reversed immunosuppressive infiltration, nominating POSTN-directed strategies to potentiate ICB.

Ovarian cancer is the most lethal malignancy of the female reproductive system worldwide. Chemoresistance, particularly platinum resistance, is a major factor limiting improvement in prognosis, and its underlying mechanisms involve complex regulation of and escape from multiple programmed cell death pathways in cancer cells. Disulfidptosis is triggered by high expression of solute carrier family 7 member 11 (SLC7A11) under glucose starvation and shares upstream regulatory nodes with ferroptosis. Necrosis by sodium overload is driven by sodium ion overload mediated by transient receptor potential cation channel subfamily M member 4 (TRPM4), but its role remains to be further investigated. Other programmed cell death pathways are interwoven into a dynamic regulatory network through key regulatory molecules such as tumor protein p53, the caspase family, cysteine-aspartic proteases, and glutathione. Autophagy can inhibit pyroptosis; ferroptosis and pyroptosis can synergistically amplify cell-killing effects through the reactive oxygen species/NOD-like receptor thermal protein domain-associated protein 3 axis; ferroptosis and cuproptosis share the glutathione metabolic axis; and the interaction between ferroptosis and disulfidptosis can shift from antagonism to synergy under specific metabolic stress. Ferroptosis and necrosis by sodium overload mutually promote each other through cascades involving adenosine triphosphate depletion, reactive oxygen species accumulation, and mitochondrial damage. PANoptosis can overcome cancer-cell resistance to a single mode of cell death through the simultaneous activation of multiple cell death pathways. A comprehensive review of the roles and interactive networks of various programmed cell death modalities, including disulfidptosis, necrosis by sodium overload, apoptosis, autophagy, necroptosis, pyroptosis, ferroptosis, cuproptosis, and PANoptosis, in platinum resistance in ovarian cancer is expected to provide a solid theoretical basis and potential translational directions for reversing platinum resistance and optimizing clinical treatment strategies.

Immune checkpoint inhibitors (ICIs), particularly those targeting the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) axis, have emerged as potential tools beyond cancer immunotherapy in people with HIV (PWH). In the setting of effective antiretroviral therapy (ART), chronic inflammation, T-cell exhaustion, and persistent viral reservoirs remain major obstacles to durable HIV remission or cure. Accumulating evidence suggests that ICIs may modulate these processes by reversing latency, enhancing HIV-specific immune responses, and contributing to reservoir regulation and immune restoration. In this review, we summarize current evidence on the role of ICIs in HIV infection, with a focus on reservoir regulation and immune restoration. We discuss the biological rationale for checkpoint blockade in chronic HIV infection and review available data from preclinical models, clinical studies in PWH with cancer, exploratory trials in non-cancer populations, and combination cure strategies. We also address recent findings on proviral landscape changes and key safety considerations. Overall, ICIs represent a promising but still limited component of HIV cure-oriented strategies. Their effects on reservoir dynamics and immune restoration remain heterogeneous, and further progress will require safer dosing approaches, biomarker-guided patient selection, standardized reservoir assessment, and well-designed clinical trials.

This work aims to design and characterize a novel bifunctional small molecule that simultaneously targets PD-L1 and CD73 to enhance the therapeutic efficacy of tumor immunotherapy.

Immune checkpoint inhibitor (ICI) therapy has become standard of care for late stage non-small cell lung cancer (NSCLC), producing durable responses in a subset of patients. However, inflammatory side eKects termed immune-related adverse events (irAEs) occur in up to 40% of ICI-treated NSCLC patients. Current approaches to alleviate irAEs include treatment with immune-suppressing corticosteroids. However, these treatments may undermine the eKicacy of ICIs by suppressing both the irAE and the anti-tumour immune response. To identify more specific therapeutic targets, a better understanding of the complex immunopathology underlying the development of irAEs in NSCLC is required.

Ubiquitin-specific protease 28 (USP28) is a deubiquitinating enzyme initially identified as a regulator that stabilizes p53 and c-MYC in response to DNA damage stress. Beyond its role in maintaining genomic integrity and cell cycle checkpoints, USP28 is implicated in diverse pathological processes. In various solid tumors, including lung, pancreatic, ovarian, and hepatocellular carcinomas, USP28 is markedly upregulated; it promotes proliferation, metabolic reprogramming, invasion, and therapeutic resistance by stabilizing oncoproteins such as c-Myc, STAT3, and SOX9. Conversely, in specific contexts like breast cancer and certain melanomas, USP28 deficiency drives malignant progression, revealing a context-dependent functional duality. These findings underscore the complexity of USP28 signaling and highlight its potential as a therapeutic target for precision medicine. This review summarizes the molecular characteristics and physiological functions of USP28, its context-dependent roles in neoplastic diseases, and its translational implications for targeted therapy and biomarker discovery.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of lung cancer (LC), offering durable responses in non-small cell lung cancer (NSCLC) and, to a lesser extent, small cell lung cancer (SCLC). Nevertheless, clinical outcomes remain highly heterogeneous, with many patients experiencing primary or acquired resistance and/or immune-related adverse events (irAEs) that impair their quality of life and treatment adherence. The human microbiome, particularly in the gut and oral compartments, has emerged as a critical modulator of systemic antitumor immunity and a promising noninvasive predictive biomarker for ICI efficacy and toxicity. This narrative review synthesizes the current evidence on microbiome composition, diversity, and function in patients with LC receiving ICIs as monotherapy, dual blockade, or in combination regimens, as well as clinically relevant biomarkers associated with treatment response and toxicity. Higher gut microbial alpha diversity and enrichment of beneficial taxa (e.g., Akkermansia muciniphila, Faecalibacterium prausnitzii, and certain Firmicutes) are consistently linked to improved progression-free survival (PFS) and overall survival (OS), mediated by microbial metabolites such as short-chain fatty acids and inosine, which enhance T-cell priming, tumor microenvironment remodeling, and gut-lung axis communication. Microbiome-disruptive exposures, particularly antibiotics and proton pump inhibitors (PPIs), induce dysbiosis and are strongly associated with poorer survival outcomes. Mechanistic insights from preclinical models and clinical cohorts, alongside clinical confounders, underscore the complementary role of the microbiome relative to established markers such as programmed death-ligand 1 (PD-L1) and tumor mutational burden. Prospective standardization of metagenomic profiling and microbiome-modulating interventions represents a key next step in translating these findings into personalized immunotherapy strategies for LC.

The extensive expression of STING in patients with non-small cell lung cancer (NSCLC) is closely associated with overall survival and other factors. Activation of the STING pathway can suppress NSCLC. However, the clinical translation of STING agonists remains hindered by challenges such as off-target effects, metabolic instability, and suboptimal pharmacokinetics.

Tolerance of chemotherapy is a special concern in older patients, owing to comorbidities and lower physical reserves compared with younger patients. There has been no substantial research done locally regarding chemotherapy tolerance.

Doxorubicin is widely used in veterinary oncology but carries a risk of cumulative cardiotoxicity. Serial echocardiographic evaluation is commonly used to monitor dogs receiving potentially cardiotoxic chemotherapy; however, evidence remains limited regarding which indices best capture early longitudinal systolic changes. Conventional monitoring relies largely on fractional shortening and M-mode estimated ejection fraction, which are based on geometric assumptions and may have limited sensitivity for subtle systolic change. This study evaluated whether Simpson-derived left ventricular ejection fraction better captures longitudinal echocardiographic systolic changes than conventional indices in dogs receiving doxorubicin-based chemotherapy. Twenty-nine client-owned dogs were prospectively enrolled, including 23 females and 6 males, with a median age of 10.0 years (IQR, 7.0-11.0) and median body weight of 13.2 kg (IQR, 7.0-21.6). Twelve dogs received doxorubicin as monotherapy and 17 received combination protocols. Echocardiography was performed before the first cycle (D0) and after three consecutive cycles (D1, D2, D3).

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Current tyrosine kinase inhibitors (TKIs) targeting oncogenic KIT and PDGFRA have improved patient outcomes, yet off-target toxicities and drug resistance mutations remain major clinical challenges. Many approved TKIs, often repurposed from other cancer indications, harbor diverse hinge-binding motifs that limit activity against resistance mutations clustering in the ATP-binding pocket of the kinase domain. Here, we describe a structure-based scaffold-hopping strategy to design kinase inhibitors with selectivity for mutant KIT/PDGFRA. Using structure-activity relationship (SAR) studies and 14 determined co-crystal structures, including a structure of the PDGFRA-G680R solvent-front mutation, we define key molecular interactions underlying resistance and inhibitor selectivity. Our lead 6,7-quinazoline-based inhibitors show high potency against clinically relevant KIT/PDGFRA mutations and effectively suppress downstream signaling. These compounds provide selective chemical tools to interrogate resistance mechanisms, and the PDGFRA-G680R structure shows the molecular basis for targeting solvent-front mutations across oncogenic kinases.

The tumor microbiota critically shapes responses to immunotherapy; however, the mechanisms by which specific microbial species drive immune checkpoint blockade (ICB) resistance in gastric cancer (GC) remain poorly defined.

Remote examinations have become increasingly common in Dentistry, especially with the use of applications. This preliminary cross-sectional study evaluated the accuracy of remote examination of oral mucositis (OM) and severe oral mucositis (SOM) using photos obtained through the Telepediatric Dentistry in Oncology (TON) application, comparing its results with the in-person clinical examination (gold standard). A total of 21 pediatric patients (13 boys, 8 girls; mean age 9.05 ± 3.46 years) undergoing chemotherapy were examined, totaling 28 in-person examinations and 224 photographic images assessed remotely by four calibrated dentists (Kappa > 0.7). The photos covered eight oral cavity sites (lips, right and left buccal mucosa, tongue dorsum, lateral tongue, palate, and floor of the mouth) and were analyzed for the presence or absence of OM and SOM. Among the 28 examinations, 11 presented OM and 3 presented SOM. The remote examination identified all positive cases (sensitivity 100%; 95%CI: 0.741-1), while specificity was 59% for OM, reflecting the occurrence of false positives, especially in the lips and buccal mucosa. Agreement between remote examiners and the gold standard ranged from 0.17 to 1.0, depending on the region and evaluator, being higher in the tongue dorsum, lateral tongue, and floor of the mouth. The results indicate that remote examination via TON may be feasible and has the ability to detect OM and SOM, potentially serving as a complementary tool in dental monitoring of children and adolescents undergoing oncology treatment, particularly when in-person examination is not possible.

Anthyllis henoniana leaves and flowers were subjected to fractionated extraction using cyclohexane (CYHA), dichloromethane (DCM), ethyl acetate (EtOAc) and methanol (MeOH). The leaves-MeOH extract showed the highest yield and total polyphenol contents (TPC) compared to the flowers. The strongest antiradical activity (IC50 = 7.7 µg/mL) was recorded for the leaves compared to flowers (>50 µg/mL). The HPLC-DAD analysis showed the presence of eight and twelve bioactive compounds in the leaf and flower extracts, respectively. The flowers-CYHA extract exhibited the best anti-5-lipoxygenase (anti-5-LOX) activity (IC50 = 15 µg/mL) compared to the leaves (IC50 = 42 to 47 µg/mL). Anthyllis henoniana leaves showed greater anti-acetylcholinesterase (anti-AChE) activity than the flowers. The leaves-DCM fraction induced 60 and 70% cell growth inhibition against MCF-7 and HCT-116, respectively. Furthermore, the molecular docking investigations supported the in vitro antioxidant and anti-5-LOX patterns, revealing that the identified compounds exhibited low binding energies and interacted effectively within the novel human peroxidase (PDB:1PRX) and the crystal structure of soybean lipoxygenase-B (PDB: 2IUJ) enzymes, respectively. The obtained results indicated that the leaves-MeOH extract was the most enriched in polar compounds with high antioxidant and cytotoxic capacities, whereas the flowers-CYHA extracts accumulated nonpolar compounds of an effective anti-inflammatory capacity.

Olaparib has demonstrated clinical benefit in patients with metastatic castration-resistant prostate cancer (mCRPC) harboring BRCA pathogenic or likely pathogenic variants (PVs) in randomized clinical trials; however, multicenter real-world data in Japanese patients remain limited.

The preservation of the tumor immune microenvironment (TIME) ex vivo is essential for investigating tumor-immune interactions and developing effective immunotherapies. However, current culture models often fail to maintain autologous immune cells or support high-throughput testing. To overcome these limitations, we establish and validate a novel miniaturized-tumor culture (MTC) platform.

Doxorubicin (DOX) is a potent chemotherapeutic agent whose antitumor benefits are limited by a well-recognized, dose-dependent cardiotoxicity. While previous studies have implicated inflammatory pathways in DOX-induced cardiomyopathy (DIC), the role of CCR2 in this process remains incompletely defined. This study aims to investigate whether CCR2 deficiency confers cardioprotection against DIC and to uncover the molecular mechanisms involved.

The combination therapies are significantly more effective than monotherapies in enhancing anticancer efficacy, reducing drug-related toxicity, and lowering the risk of drug resistance in cancer treatment. However, achieving precise delivery of the drugs to the tumor site remains a major challenge. With the deepening exploration of surface-engineered nanocarriers, ligand-modified liposomal drug delivery systems (LLDDS) are constructed by integrating the active-targeting properties of functional ligands (such as peptides, glycans, and aptamers) with the inherent advantages of liposomes. LLDDS show promise for exhibiting strong tumor-targeting capability, improving pharmacokinetics, biodistribution, and therapeutic efficacy of anticancer agents, such as chemotherapy drugs, and enabling the multifunctional integration of multiple therapeutic strategies. This review summarizes the development of liposomes and ligand-mediated surface modification strategies. More significantly, the development of multifunctional liposomes, targeted delivery, improved anticancer effectiveness, and possible anticancer mechanisms are highlighted in the discussion of LLDDS's recent advancements for integrated therapy approaches in a variety of malignancies. Lastly, the potential and difficulties of clinical translation in this ever-evolving area are examined.