Emerging evidence highlights the critical role of metabolic pathways in breast cancer (BC) progression. Here, we developed a butyrate metabolism-specific gene (BMRG) signature to predict clinical outcomes and immunotherapy responses in BC, providing a novel pathway-focused prognostic tool. Using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we identified 102 butyrate metabolism-related differentially expressed genes (DEGs) through the intersection of DEGs, WGCNA-derived key module genes, and BMRGs. Univariate Cox followed by least absolute shrinkage and selection operator (LASSO) analysis identified nine genes to construct a prognostic signature, which served as an independent prognostic factor. Risk stratification revealed distinct immune microenvironment and mutation landscapes between subgroups, with risk scores strongly correlating with immune checkpoint expression. The signature exhibited robust prognostic performance, with AUC values for 3-, 5-, and 7-year overall survival ranging from 0.65-0.69 in TCGA and 0.57-0.77 in independent GEO cohorts. Protein-protein interaction analysis identified ACSL1 as a key hub gene, and functional validation confirmed that ACSL1 knockdown suppressed BC cell proliferation and migration. Our findings establish this novel nine-gene butyrate metabolism-specific signature as a promising prognostic biomarker and potential therapeutic target for BC, providing a metabolism-focused perspective for personalized BC management.

Hepatocellular carcinoma (HCC) is one of the most lethal tumors, and effective treatments for HCC, especially metastatic HCC, are lacking. Chimeric antigen receptor (CAR)-T-cell therapy is considered a promising development in cancer treatment, but to date, CAR-T-cell therapy for solid tumors remains limited. Matrix metalloproteinase 14 (MMP14), the only membrane-bound collagenase, is highly expressed in HCC and other solid tumors and plays critical roles in invasion and metastasis.

Here, we aimed to determine whether CAR-T cells targeting MMP14 could effectively treat HCC. CAR-T cells were designed with peptide G (PG) to specifically recognize MMP14. These cells were evaluated for their cancer-killing efficacy in vitro under MMP14-dependent conditions and tested for antitumor activity in a subcutaneous xenograft liver cancer model. Additionally, a spontaneous liver cancer metastasis model was employed to assess the impact of PG-CAR-T cells on metastasis suppression through circulating tumor cells (CTCs) elimination. The safety profile of PG-CAR-T cells was further investigated in both murine and nonhuman primate models.

PG-CAR-T cells demonstrated efficient MMP14-dependent killing of cancer cells in vitro and exhibited antitumor effects in the subcutaneous xenograft liver cancer model. In the metastasis model, PG-CAR-T cells significantly inhibited metastasis by eliminating CTCs. Furthermore, PG-CAR-T cells showed a favorable safety profile in both mice and nonhuman primates.

These data support the PG-CAR-T cells for clinical trial of liver cancer.

This study aims to evaluate the potential of Trefoil Family Factor 1 (TFF1) as a biomarker for the diagnosis and prognosis of retinoblastoma.

Our protocol was prospectively registered on PROSPERO (CRD420251126954). On July 08, 2025, we conducted a comprehensive literature search across PubMed, Scopus, Web of Science, Embase, Cochrane, and Google Scholar. We included all studies that measured TFF1 expression in retinoblastoma patients and assessed its potential as a biomarker for disease severity. The primary outcomes were laterality, sex, and age at diagnosis. Secondary outcomes included tumor invasion and disease staging. Statistical analysis was performed using RStudio. A random-effects model was used for the analysis, and heterogeneity was assessed using the I². The risk of bias for the included studies was evaluated using the Newcastle-Ottawa Scale for Retrospective cohort studies, while the NIH Quality Assessment Tool for Case Series Studies was used for case series studies.

Of the 152 articles initially identified, only 5 met the inclusion criteria, comprising a total of 521 patients with retinoblastoma. Patients with higher TFF1 expression exhibited a significantly lower risk of bilateral involvement (RR = 0.57; 95% CI: 0.39, 0.84; p = 0.0041) and a significantly higher association with being diagnosed after the age of 3 years (RR = 4.26; 95% CI: 1.33, 13.64; p = 0.01). No statistically significant associations were observed with sex (RR = 0.89; 95% CI: 0.74,1.07; p = 0.2), choroid invasion (RR = 0.99; 95% CI: 0.9,1.08; p = 0.76) or optic nerve invasion including no invasion (RR = 0.75; 95% CI: 0.47,1.21; p = 0.24), pre-laminar invasion (RR = 1.13; 95% CI: 0.75,1.7; p = 0.55) or post laminar invasion (RR = 1.04; 95% CI: 0.89,1.21; p = 0.61).

Retinoblastoma tumors with higher TFF1 expression were associated with a reduced risk of bilateral involvement and an increased likelihood of diagnosis after the age of 3 years. Although the associations with choroidal and optic nerve invasion were not statistically significant, TFF1 remains a promising candidate biomarker for the diagnosis and prognosis of retinoblastoma, particularly due to its absence in normal ocular tissue. Further high-quality studies are required to validate the clinical utility of TFF1 as a reliable diagnostic and prognostic marker in retinoblastoma.

TAK-500 is a novel immune cell-directed antibody-drug conjugate (iADC) composed of TAK-202, an anti-CCR2 monoclonal antibody, conjugated to the STING agonist dazostinag (TAK-676), and is designed to stimulate antitumor immunity by reprogramming CCR2-positive monocytes. To support clinical translation, we developed a population pharmacokinetic (PK)-receptor occupancy (RO) model that leveraged both preclinical and clinical data from the parental antibody. In cynomolgus monkeys, TAK-500 displayed nonlinear, target-mediated disposition with dose-dependent CCR2 RO and monocyte redistribution. A 2-compartment PK model confirmed that TAK-500 total antibody and TAK-202 exhibited comparable PK profiles in monkeys, suggesting translational concordance. In humans, TAK-202 demonstrated nonlinear PK with greater-than-dose-proportional exposure, which was not captured by allometric scaling from monkeys but provided a critical basis for model development. We established a population PK-RO model of TAK-202 in humans and integrated it with cynomolgus TAK-500 data to project human PK and RO across doses of 50-500 μg/kg. Simulations (n = 1000) predicted dose‑dependent decreases in clearance, from 40 to 31 mL/h for total antibody and from 148 to 124 mL/h for conjugated payload (median values in a 70‑kg adult), respectively. Corresponding terminal half-lives were estimated at 114-118 h for total antibody and 30-60 h for conjugated payload. These findings demonstrate the feasibility of predicting TAK-500 PK and RO in humans by integrating preclinical and parental antibody clinical data, providing a quantitative framework for first-in-human dose selection of immune cell-directed ADCs. Trial Registration: Clinical trials: NCT04420884, NCT04879849.

Substance use spans a continuum from occasional use to hazardous use and clinically defined substance use disorders, and it can shape outcomes across the cancer care continuum. This structured narrative review synthesises evidence on how alcohol, tobacco, cannabis and opioids relate to cancer outcomes relevant to supportive care, including diagnostic timing, adherence, toxicity, symptom burden and survival. Methods We searched PubMed, Scopus and Web of Science for peer-reviewed studies published between January 2010 and April 2025 and narratively synthesised findings given heterogeneity in study designs and exposure definitions. Results Heavy or hazardous alcohol use and continued tobacco use are well-established carcinogenic exposures and are associated with delayed diagnosis, poorer treatment adherence, greater toxicity and inferior survival in observational studies. Evidence for cannabis and opioids is heterogeneous and predominantly observational; interpretation is limited by variable exposure measurement, including product composition and route of administration and dose, as well as polysubstance use, confounding and reverse causation. For opioids specifically, it is essential to distinguish analgesic use for cancer pain, physiological dependence and opioid use disorder. Conclusions To improve patient-centred outcomes, supportive oncology should embed routine screening, brief interventions and clear referral pathways, while implementing integrated oncology-addiction care models tailored to symptom burden and patient-reported outcomes. Future research should prioritise standardised exposure definitions, prospective longitudinal designs and evaluation of integrated care models in supportive oncology.

Reprogramming of lipid metabolism and cyclic GMP‒AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling is associated with cancer development. However, whether and how fatty acid metabolism regulates the cGAS‒STING pathway in colorectal cancer (CRC) remains to be elucidated. In this study, we found that short-chain acyl-CoA dehydrogenase (ACADS) is aberrantly deficient in CRC cells and is associated with cancer progression in human patients. We further revealed that ablation of ACADS promoted CRC progression by orchestrating the cGAS‒STING signaling-dependent immunosuppressive tumor microenvironment (TME) in mouse xenografts and AOM/DSS-induced CRC models. Mechanistically, ACADS deficiency suppressed cGAS‒STING signaling by inhibiting mtDNA leakage in a nonmetabolic manner. ACADS binds to and inhibits mitochondrial DNMT1 (mito-DNMT1)-dependent mtDNA methylation, thereby stabilizing mtDNA and inhibiting its leakage. Genetic and pharmacological modulation of mito-DNMT1 restored ACADS-regulated mtDNA leakage, cGAS‒STING signaling, and CRC progression. Importantly, strong correlations between ACADS, mito-DNMT1, and STING signaling and the immune TME were found in patients with CRC. Furthermore, we screened and identified an old drug, hypericin, as an ACADS-binding compound that upregulates ACADS expression. Hypericin treatment can mimic ACADS overexpression-regulated pathways, ultimately improving the immune TME and suppressing CRC growth. These findings highlight a previously undiscovered ACADS/mito-DNMT1 complex that links fatty acid metabolism reprogramming to mtDNA methylation and cGAS‒STING signaling-dependent antitumor immunity.

This study aims to investigate the effects of long noncoding RNA myocardial infarction-associated transcript (lncRNA MIAT) targeting miR-361-3p on the proliferation, invasion, and apoptosis of hepatocellular carcinoma (HCC) cells. The expression levels of lncRNA MIAT and miR-361-3p were examined in both cancerous and adjacent non-tumorous tissues of HCC patients. Additionally, their expression was analyzed in THLE-2 and MHCC97L cells. MHCC97L cells were transfected to observe changes in relevant mRNA expression and alterations in cell proliferation, invasion, and apoptosis. Compared with adjacent non-tumorous tissues, cancerous tissues exhibited increased levels of lncRNA MIAT mRNA and decreased levels of miR-361-3p (P < .05). Elevated transcription levels of lncRNA MIAT were more prevalent in patients with lymph node metastasis and advanced TNM staging (P < .05). In MHCC97L cells, compared with THLE-2 cells, there was an increase in lncRNA MIAT mRNA and a decrease in miR-361-3p (P < .05). LncRNA MIAT and miR-361-3p were found to have potential binding sites and exhibit target regulation. Cells in the miR-NC group showed no significant changes in all indicators compared with the negative control group (P > .05). Conversely, cells with low expression of lncRNA MIAT and cyclin D1 mRNA and decreased cell proliferation and invasion numbers showed increased expression of miR-361-3p and phosphatase and tensin homolog mRNA and higher apoptosis rates (P < .05). The group with elevated expression levels demonstrated contrasting patterns (P < .05). LncRNA MIAT is upregulated in HCC tissues. Silencing lncRNA MIAT can elevate miR-361-3p levels, inhibiting the proliferation and invasion of MHCC97L cell structures and promoting apoptosis.

Esophageal squamous cell carcinoma (ESCC) is among the most lethal malignancies worldwide, with a five-year survival rate below 20%. Ferroptosis-a regulated form of cell death driven by iron-dependent lipid peroxidation-has emerged as a promising therapeutic strategy, yet its regulation in ESCC remains poorly understood. We investigated the role of tripartite motif-containing 31 (TRIM31), an E3 ubiquitin ligase, in ESCC progression and ferroptosis.

TRIM31 expression was significantly elevated in ESCC tissues compared with normal esophageal tissues (The Cancer Genome Atlas and Genotype-Tissue Expression datasets; p < 0.001) and correlated with advanced Tumor, Node, and Metastasis (TNM) stage (p = 0.004), lymph node metastasis (p = 0.024), and poor overall survival (p = 0.0027). Functional assays revealed that TRIM31 knockdown reduced ESCC cell proliferation, impaired colony formation, and suppressed migration (p < 0.01). In vivo, TRIM31 silencing decreased xenograft tumor volume by over 70% and Ki-67 expression by 73%. Mechanistically, TRIM31 directly interacted with VDAC1 via its coiled-coil domain, promoting VDAC1 ubiquitination and proteasomal degradation. This interaction inhibited ferroptosis, as evidenced by increased lipid reactive oxygen species, elevated intracellular Fe²⁺ levels, and mitochondrial damage upon TRIM31 knockdown. Conversely, TRIM31 overexpression attenuated ferroptosis induced by RSL3. We further identified hepatocyte nuclear factor 4 alpha as a transcriptional activator of TRIM31, binding to its promoter region. Importantly, TRIM31 knockdown synergized with the ferroptosis inducer imidazole ketone erastin, achieving a 90% reduction in tumor growth without significant toxicity.

TRIM31 promotes ESCC progression by degrading VDAC1 and suppressing ferroptosis. Targeting TRIM31 enhances ferroptosis-based therapy and represents a novel, clinically actionable strategy for ESCC treatment. Antioxid. Redox Signal. 44, 550-571.

Controlling the proliferation and immune evasion of cancer cells can lead to effective strategies for cancer treatment. Thymoquinone, a bioactive compound derived from Nigella sativa exhibits a potent anti-tumor activity. It can be used as a therapeutic approach because it stabilizes the G-quadruplex structure in the promoter regions of oncogenes. This study aims to investigate the effects of thymoquinone on CD55, an inhibitor of the complement system, and CD114, which is involved in cancer cell proliferation. Real-time PCR and Western blot were conducted to verify the expression of CD55 and CD114 in patients' tumor samples, HMEC cells, MCF-7 cells, and MCF7-cancer stem cells (MCF7-CSCs). MCF-7 cells were treated with thymoquinone, and their biological behavior was evaluated using proliferation, migration, and wound-healing assays. The result indicated that CD55 and CD114 were induced among the patient's samples. The same result is followed by MCF-7 cells and MCF7-CSCs. Treatment of MCF-7 and MCF7-CSCs with thymoquinone effectively downregulated CD55 and CD114 and suppressed the stemness markers Sox2 and Nanog. Promoter analysis revealed the putative G-quadruplex sequences in the CD55 and CD114 genes. Thymoquinone binds to them at the CD55 and CD114 promoters, thereby limiting mRNA expression. Additionally, the inhibition of their expression reduced cell movement and growth, as verified by biological assays. In summary, treating breast cancer cells with thymoquinone could stabilize the G-quadruplex structure on the promoter regions of CD55 and CD114 and hinder their mRNA expression. Therefore, restoring immune recognition and inhibition of proliferation. Hence, thymoquinone could be a potent target for breast cancer therapeutics.