Thimerosal is a mercury-containing preservative widely used in vaccines. This study aimed to investigate its potential antitumor effects and mechanisms in solid malignancies, particularly colorectal cancer (CRC) and melanoma.

A combination of in vitro and in vivo approaches was employed. Cell proliferation, apoptosis, migration, and invasion were assessed using Cell Counting Kit-8 (CCK-8), colony formation, ATP viability, Western blotting, flow cytometry, wound-healing and Transwell assays. Subcutaneous, lung metastases, and Azoxymethane/Dextran Sulfate Sodium Salt (AOM/DSS)-induced colitis-associated CRC models were established to examine antitumor efficacy and safety. The functional role of mercury ions was validated using structural analogues. Mechanistic studies included RNA sequencing, Western blot, and immunohistochemical analysis of CD8⁺ T cell infiltration. The synergistic effect with programmed cell death protein 1 (PD-1) antibody therapy was also evaluated.

Thimerosal potently inhibited tumor growth (with IC₅₀ values ranging from 0.1 to 1 μM in vitro) and significantly prolonged survival without overt toxicity in vivo. Mechanistically, mercury ions were identified as critical functional sites mediating Thimerosal's antitumor effects. Specifically, Thimerosal inhibited the phosphorylation of Janus kinase 1(JAK1) and signal transducer and activator of transcription 3 (STAT3). Furthermore, it enhanced the infiltration of CD8⁺ T cells into the tumor microenvironment and synergistically augmented the efficacy of anti-PD-1 therapy.

Thimerosal exerts dual antitumor roles by direct JAK1/STAT3 inhibition and immune modulation via CD8⁺ T cell recruitment. It represents a promising repurposed drug and immunotherapeutic adjuvant for CRC and melanoma.

Parasitic infections are increasingly recognized as contributors to cancer development, yet the underlying oncogenic mechanisms remain insufficiently understood. Growing evidence from molecular oncology, immunology, and microbiome research suggests that chronic parasitic infections may drive tumorigenesis through sustained inflammation, deregulated signaling pathways, genomic instability, and the release of parasite-derived exosomes that reshape the tumor microenvironment. These insights underscore the need to integrate parasitology with cancer biology to understand infection-associated malignancies better. The aim of this narrative review is to synthesize current knowledge on how selected parasites contribute to cancer development and to highlight emerging therapeutic and diagnostic opportunities. We examine pathogens such as Schistosoma haematobium, Opisthorchis viverrini, Toxoplasma gondii, Plasmodium falciparum, and Leishmania spp., detailing their roles in chronic inflammation, immune modulation, and interactions with tumor-associated immune cells. The review further discusses parasite-induced immunosuppression, coinfections, and their cumulative impact on cancer risk. Additionally, we explore novel therapeutic approaches, including pathway inhibitors, epigenetic drugs, microbiome modulation, and engineered parasites. Future perspectives emphasize parasite-based immunotherapies, long-term epigenetic consequences of infection, and AI-driven multi-omics strategies for identifying oncogenic signatures. This review integrates advances from parasitology and oncology to provide new insights into biomarkers, targeted therapies, and mechanisms of infection-induced tumorigenesis. The literature search covered studies indexed in PubMed, Scopus, and Web of Science up to July 2025.

The gut microbiome has emerged as a critical modulator of cancer immunotherapy response. However, the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer (PC) remain not fully explored. The study aimed to explore how gut metabolites regulate death-ligand 1 (PD-L1) blockade via exosomes and boost immune checkpoint inhibitors (ICIs) in PC.

We recruited 70 PC patients to set up into five subgroups. The integrated multi-omics analysis was performed. In parallel, we validated the function of gut microbiome-associated metabolites on PD-L1 production and immunotherapy treatment efficacy in PC cell lines and transgenic adenocarcinoma of the mouse prostate (TRAMP) models.

We identified two metabolites, 16(R)-Hydroxyeicosatetraenoic acid (16(R)-HETE) and 6-Keto-Prostaglandin E1 (6-Keto-PGE1), that positively correlated with the plasma exosomal PD-L1 levels. The in vitro experiments found that both 16(R)-HETE and 6-Keto-PGE1 can enhance PD-L1 expression at the mRNA, protein, and exosome levels in both human and mouse PC cell lines, which were also validated in vivo based on subcutaneous mouse models. Both metabolites significantly promoted the anti-PD-L1 efficacy against PC in situ on a TRAMP mouse model.

Targeting the "gut-tumor metabolic axis" is a promising strategy to improve the efficacy of immune checkpoint inhibitors in tumors.

Prostate cancer (PCa) remains a major cause of cancer-related mortality in men, largely due to therapy resistance and metastatic progression. Increasing evidence highlights the tumor microenvironment (TME), particularly cancer-associated fibroblasts (CAFs), as a critical determinant of disease behavior. CAFs constitute a heterogeneous population originating from fibroblasts, mesenchymal stem cells, endothelial cells, epithelial cells undergoing epithelial-mesenchymal transition (EMT), and adipose tissue. Through dynamic crosstalk with tumor, immune, endothelial, and adipocyte compartments, CAFs orchestrate oncogenic processes including tumor proliferation, invasion, immune evasion, extracellular matrix remodeling, angiogenesis, and metabolic reprogramming. This review comprehensively summarizes the cellular origins, phenotypic and functional heterogeneity, and spatial distribution of CAFs within the prostate TME. We further elucidate the molecular mechanisms by which CAFs regulate PCa progression and therapeutic resistance, and critically evaluate emerging strategies to therapeutically target CAF-mediated signaling, metabolic, and immune pathways. By integrating recent advances from single-cell and spatial transcriptomics (ST), our objective is to provide a holistic framework for understanding CAF biology and to highlight potential avenues for stromal reprogramming as an adjunct to current PCa therapies.

Immunotherapy based on immune checkpoint blockade (ICB) has become a key treatment for melanoma. However, the increasing number of cases of melanoma resistant to immunotherapy highlights the need to develop methods to overcome this resistance. This study aims to collect the most recent information on melanoma immunotherapy, discuss potential strategies to overcome resistance to immunotherapy, and identify areas that require further analysis.

To achieve this goal, scientific publications from 2021-2024 available in PubMed and Google Scholar databases were analyzed. The databases were searched using the following terms: "melanoma", "immunotherapy", "Immune Checkpoint Blockade", and "immunoresistance".

The results of preclinical and early-stage clinical research indicate the potential application of tank-binding kinase 1 (TBK-1), fecal microbiota transplant (FMT), Toll-like Receptor 9 (TLR9), lipid nanoparticles (LNPs) containing a stimulator of an interferon gene agonist (STING), BRAF inhibitors, Lymphocyte Activation Gene (LAG-3), T-Cell Immunoglobulin and ITIM Domain (TIGIT), and oncolytic viruses (OVs) as potential methods to enhance melanoma sensitivity to ICB.

To optimize immunotherapy, further research is needed to determine the detailed mechanisms of action, safety profiles, tolerability, and precise patient selection criteria for methods capable of overcoming melanoma's immunoresistance.

The prolonged and intricate history of oncological treatments has transitioned significantly since the introduction of chemotherapy. Substantial therapeutic benefits in cancer therapy have been achieved by the integration of conventional treatments with molecular biosciences and omics technologies. Human epidermal growth factor receptor, hormone receptors, and angiogenesis factors are among the established therapies in tumor reduction and managing side effects. Novel targeted therapies like KRAS G12C, Claudin-18 isoform 2 (CLDN18.2), Trophoblast cell-surface antigen 2 (TROP2), and epigenetic regulators emphasize their promise in advancing precision medicine. However, in many cases, the resistance mechanisms associated with these interventions render them ineffective in carrying out their functions. The purpose of this review is to provide a comprehensive and up-to-date examination of both established and emerging drug targets and mechanisms of treatment resistance in oncology. This review seeks to elucidate recent advancements, address persisting challenges, and explore opportunities for innovative developments in cancer target research. Additionally, it explores the growing role of artificial intelligence in reshaping cancer drug discovery and development frameworks as potential avenues for future research. In conclusion, innovative approaches in oncology, supported by pharmacological research, ongoing clinical trials, molecular biosciences, and artificial intelligence, are poised to significantly transform cancer treatment.

Breast cancer is one of the most prevalent malignancies among women and comprises a heterogeneous spectrum of molecular subtypes with distinct biological behaviors. Among various regulatory molecules, sphingolipids play pivotal roles in dynamically modulating fundamental cellular processes such as proliferation, apoptosis, and metastasis through metabolic interconversions, including phosphorylation, glycosylation, and the generation of sphingosine-1-phosphate. This review aims to elucidate the mechanisms through which sphingolipid metabolism orchestrates cancer cell fate and drives breast cancer progression. Particular emphasis is placed on the balance between proapoptotic ceramides and pro-survival metabolites, such as sphingosine-1-phosphate, which collectively influence tumor growth and the therapeutic response. Additional sphingolipid species, including glucosylceramide and gangliosides (GD2, GD3, GM1, and GM3), have also been implicated in promoting breast cancer development. Furthermore, sphingolipid-based therapeutic strategies, including immunotherapy and antibody therapy, are discussed. By providing a comprehensive overview of sphingolipid metabolism, this review aims to identify novel therapeutic targets that may help overcome treatment resistance and improve clinical outcomes in breast cancer.

Human papillomavirus (HPV) infection is a major global health concern due to its association with various cancers, particularly cervical and head and neck squamous cell carcinomas. High-risk HPV types, such as HPV16 and HPV18, employ oncoproteins E6 and E7 to disrupt host cell regulatory pathways, promote immune evasion, and facilitate malignant transformation. Natural killer (NK) cells, critical components of innate immunity, play a pivotal role in surveilling and eliminating HPV-infected cells. However, HPV-mediated immune evasion mechanisms, including downregulation of MHC-I, suppression of chemokine signaling (e.g., CXCL14), and upregulation of inhibitory molecules (e.g., TIGIT, KLRG1), impair NK cell functionality. This review explores the intricate interactions between HPV and NK cells, highlighting the impact of HPV on NK cell infiltration, exhaustion, and receptor expression. Additionally, it discusses emerging therapeutic strategies to enhance NK cell activation, such as pharmacological agents (e.g., γ-PGA, α-GalCer), innate immune agonists (e.g., STING, RIG-I), genetic engineering (e.g., CAR-NK, iPSC-NK cells), and combination therapies with immune checkpoint inhibitors or monoclonal antibodies (e.g., cetuximab). Clinical applications, including adoptive NK cell transfer and biomarker-guided personalized immunotherapy, are also reviewed. Despite challenges like immunosuppressive tumor microenvironments and limited NK cell persistence, advancements in genetic engineering and nanoparticle delivery systems offer promising solutions. Future research should focus on integrating mechanistic insights with clinical trial design to optimize NK cell-based therapies for HPV-associated malignancies.

N6-methyladenosine (m6A) RNA methylation regulators have been implicated in colorectal cancer (CRC) progression. However, systematic evaluation using multiple machine learning approaches for prognostic prediction remains limited. This study aimed to develop and validate machine learning models for CRC prognosis based on m6A regulators and assess their potential for immunotherapy response prediction. We analyzed 1,047 CRC patients from TCGA and GEO databases (70% training, 30% validation). Twenty machine learning algorithms were systematically evaluated, with LASSO regression selecting optimal features from 27 m6A regulators. SHAP analysis provided model interpretability. Immune microenvironment characterization and immunotherapy response prediction were performed using established computational methods. LASSO regression selected eight m6A regulators (IGF2BP2, METTL3, HNRNPA2B1, METTL14, YTHDF2, VIRMA, FTO, ALKBH5) for model construction. Among 20 algorithms tested, Random Forest achieved optimal performance (training AUC = 0.895, validation AUC = 0.847). SHAP analysis identified IGF2BP2 (mean |SHAP| = 0.42) and METTL3 (mean |SHAP| = 0.36) as primary contributors to risk prediction. Risk stratification showed significant survival differences (HR = 2.41, 95% CI: 1.73-3.36, p < 0.001). Low-risk patients demonstrated enhanced immune infiltration with higher CD8⁺ T cells (17.8% vs. 10.2%, p < 0.001) and better predicted immunotherapy response rates (36.5% vs. 20.3%, p = 0.006). Our systematic machine learning analysis demonstrates that m6A regulators can effectively predict CRC prognosis and immunotherapy response. The eight-gene signature provides a practical tool for clinical risk assessment and treatment decision-making.

Cadonilimab is the first bispecific antibody independently developed in China that simultaneously targets Programmed Cell Death Protein-1 (PD-1) and Cytotoxic T Lymphocyte-Associated Antigen-4 (CTLA-4), marking a significant milestone in both clinical applications and drug development. Through its dual mechanism of action, cadonilimab blocks PD-1 and CTLA-4 signaling pathways concurrently, thereby activating T cells and enhancing antitumor immune responses. Within the tumor microenvironment, cadonilimab promotes effector T-cell infiltration while reducing nonspecific attacks on normal tissues, thus lowering the incidence of immune-related adverse events. In comparison to conventional monospecific antibodies, cadonilimab exhibits superior selectivity and safety. Multiple studies have shown that, either as monotherapy or in combination regimens, cadonilimab exhibits promising antitumor activity and tolerability in refractory solid tumors such as advanced cervical cancer, hepatocellular carcinoma, non-small cell lung cancer, and gastric cancer, with notable efficacy even in patients with low or negative PD-L1 expression. The successful development of cadonilimab not only underscores China's innovative capabilities in the field of cancer immunotherapy but also provides valuable insights for global drug development and clinical practice. However, most signals derive from phase I/II single-arm or small-sample studies with limited follow-up, and no randomized head-to-head trials have yet confirmed superiority over standard PD-1+CTLA-4 approaches. This review summarizes the mechanism of action, structural characteristics, clinical research progress, and future applications of cadonilimab, with the aim of offering a useful reference for research and clinical treatment while promoting its broader application in oncology.