The contribution of long non-coding RNAs (lncRNAs) associated with protein palmitoylation to the progression of hepatocellular carcinoma (HCC) remains largely unclear. This study sought to establish a prognostic signature based on palmitoylation-related lncRNAs and explore their functional implications in HCC.

RNA sequencing and clinical data for HCC and normal tissues were sourced from the Cancer Genome Atlas (TCGA). Pearson correlation analysis was used to identify lncRNAs that were co-expressed with palmitoylation-related genes. Univariate Cox regression was applied to select lncRNAs with prognostic value, followed by the construction of a predictive model using the least absolute shrinkage and selection operator (LASSO) regression. A focused analysis was performed on one key lncRNA, AC009403.1. Expression levels of the final nine lncRNAs included in the model were further validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR).

A prognostic model for HCC was developed using nine palmitoylation-associated lncRNAs: AC009403.1, AC010789.1, AC026402.2, AC107021.2, AC135050.6, AL353572.4, MKLN1-AS, PRRT3-AS1, and ZNF582-AS1. This model effectively stratified patients into high- and low-risk groups exhibiting significantly different overall survival (OS) and progression-free survival (PFS), with the low-risk group showing more favorable outcomes. The high-risk group was associated with an immunosuppressive microenvironment, higher tumor mutation burden (TMB), and increased sensitivity to certain chemotherapeutic drugs (e.g., Sorafenib). Finally, RT-qPCR validation revealed that all nine lncRNAs were significantly upregulated in HCC tissues.

The nine-lncRNA signature exhibits robust predictive power for HCC prognosis and provides novel insights into the mechanisms of lncRNA-regulated palmitoylation in HCC development.

The efficacy of standard 5-fluorouracil (5-FU) chemotherapy for colorectal cancer is limited by drug resistance and adverse effects, prompting research into esketamine, a potent ketamine variant with analgesic, antidepressant, and recently discovered anti-tumor properties, to determine if it can enhance 5-FU's chemosensitivity. This study investigates whether esketamine synergizes with 5-FU to enhance therapeutic efficacy in colorectal adenocarcinoma cell models.

We performed functional assays to evaluate proliferation (CCK-8), migration (wound healing), invasion (Transwell), and apoptosis (flow cytometry) in colorectal adenocarcinoma cell lines treated with 5-FU alone or in combination with esketamine. Transcriptomic profiling was conducted using RNA sequencing, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was employed to identify critical molecular targets and signaling networks. Protein-level validation of key pathway components was performed via western blotting.

Combination therapy with esketamine and 5-FU synergistically inhibited cellular proliferation, migration, and invasion while significantly inducing apoptosis compared to monotherapy. Mechanistically, esketamine potentiated 5-FU-driven AMP-activated protein kinase (AMPK) phosphorylation, leading to inhibition of both mammalian target of rapamycin (mTOR) and hyaluronan-mediated motility receptor (HMMR).

Esketamine enhances 5-FU chemosensitivity in colorectal adenocarcinoma by activating the AMPK/mTOR/HMMR signaling axis, thereby suppressing tumor progression and metastatic potential. These findings position esketamine as a potential adjunctive therapy for 5-FU-based regimens, offering the dual benefit of enhancing chemotherapeutic efficacy while addressing cancer-associated comorbidities including pain and depression.

Hepatocellular carcinoma (HCC) is an aggressive and lethal malignancy. Metabolic reprogramming dynamically remodels the tumor microenvironment (TME) and drives HCC progression. This study investigated the mechanism through which metabolic reprogramming remodels the TME in HCC.

HCC patient transcriptome data were subjected to bioinformatics analysis to identify differentially expressed genes and immune infiltration status. Immunohistochemical analysis was performed to determine the correlation between succinate dehydrogenase complex subunit A (SDHA) expression and M2 macrophage infiltration. SDHA-knockdown or SDHA-overexpressing HCC cells were used for in vitro experiments, including co-culturing, flow cytometry, and enzyme-linked immunosorbent assay. Western blotting assay, functional assays, and subcutaneous tumor model mice were used to elucidate the molecular mechanisms underlying succinate-mediated HCC cell-macrophage interactions in the TME.

Higher infiltration of M2 macrophages correlated with worse prognosis in HCC patients. SDHA was downregulated in HCC tumor tissues and showed a negative correlation with M2 macrophage infiltration. SDHA knockdown promoted M2 macrophage polarization, whereas SDHA overexpression reversed this effect. Mechanistically, SDHA deficiency in HCC cells induced succinate accumulation, which promoted M2 macrophage polarization by activating the G protein-coupled receptor 91 (GPR91)/signal transducer and activator of transcription 3 (STAT3) pathway. Concurrently, succinate stimulation enhanced mitochondrial oxidative phosphorylation in M2 macrophages, thereby promoting HCC progression. Serum succinate levels were elevated in HCC patients. The receiver operating characteristic curve analysis indicated that serum succinate is a promising diagnostic marker for HCC (area under the curve = 0.815).

SDHA deficiency leads to succinate accumulation, which promotes M2 macrophage polarization through the GPR91/STAT3 pathway, thereby facilitating HCC progression. Based on these findings, serum succinate could be a promising diagnostic biomarker for HCC.

In clinical practice, approximately 80% of prostate cancer (PC) cases are localized and can achieve favorable outcomes with appropriate treatment. Conversely, some remaining cases exhibit an aggressive phenotype or develop resistance to therapeutic interventions, leading to tumor metastasis and a poorer prognosis. When PC metastasizes to distant sites, the bone remains the predominant location, and brain metastases are regarded as exceedingly rare.

The current study focused on a rare clinical PC case that presented multiple brain metastases after prostate surgery. The patient was initially diagnosed with PC through prostate biopsy and subsequently underwent prostate debulking surgery while continuing androgen deprivation therapy, which maintained low prostate-specific antigen (PSA) levels for 4 years. However, a sudden PSA surge to 7.858 ng/mL led to the emergence of two brain metastatic tumors, which were confirmed to have originated from the prostate.

Patients with advanced PC require comprehensive evaluations to detect rare metastatic sites, such as the brain, to avoid missed diagnoses. For patients with brain metastases, a multimodal approach combining surgical resection, postoperative radiotherapy, and endocrine therapy can effectively alleviate symptoms and enhance survival.

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.