Oncology Research最新文献

Background: The Colorectal Cancer (CRC) pathogenesis and therapeutic efficacy are influenced by the gut microbiome, making it a promising biomarker for predicting treatment responses and adverse effects. This systematic review aims to outline the gut microbiome composition in individuals with CRC undergoing the same therapeutic regimen and evaluate interindividual microbiome profile variations to better understand how these differences may influence therapeutic outcomes.

Methods: Key studies investigating the microbiome's role in therapeutic approaches for CRC were searched in both PubMed and Cochrane databases on 12 and 22 March 2025, respectively. Eligible studies included free full-text English-language randomized clinical trials and human observational studies reporting on gut microbiome composition and treatment outcomes. RoB 2 and ROBINS-I were employed in the evaluation of bias for randomized trials and observational studies, respectively. Data extracted was narratively analyzed.

Results: Six studies involving a total of 361 individuals were included. Therapeutic interventions, either standard treatments and/or those targeting the gut microbiome, generally increased probiotic taxa and reduced pro-carcinogenic bacteria. However, no consistent pattern of improved clinical outcomes was observed, suggesting that treatment mechanisms, the tumor's nature, and individual characteristics play critical roles in microbiome modulation.

Conclusion: The gut microbiome holds significant potential in clinical settings. Nonetheless, further research is needed to better understand its functional aspects and to consider the influence of treatment mechanisms, the tumor's nature, and individual characteristics as modulators, in order to optimize clinical outcomes.

Acute myeloid leukemia (AML) remains a biologically heterogeneous disease with historically limited targeted therapies and poor outcomes. The development of menin inhibitors represents a promising shift, particularly for patients harboring KMT2A rearrangements (KMT2Ar) and NPM1 mutations (NPM1m). This manuscript reviews the molecular rationale of menin inhibition for aberrant homeobox/myeloid ectopic insertion site 1 (HOX/MEIS1)-driven gene expression and leukemogenesis, clinical trial outcomes, and safety data for menin inhibitors, with a focus on recently FDA-approved revumenib and several other agents in development, ziftomenib (KO-539), bleximenib (JNJ-75276617), and icovamenib (BMF-219). We also focused our discussion on future directions to include resistance mechanisms, biomarker identification and monitoring strategies, and combination therapies. Menin inhibition is now being clinically integrated into relapsed/refractory and frontline treatment settings.

Tumor metabolic reprogramming is a core hallmark of cancer, characterized by pathways such as aerobic glycolysis, aberrant lipid metabolism, and glutaminolysis that support rapid proliferation and immunosuppressive microenvironments. Circular RNAs (circRNAs) are highly stable, evolutionarily conserved non-coding RNAs that have emerged as critical modulators of these metabolic shifts. This review aims to systematically elucidate the roles and mechanisms of circRNAs in reprogramming tumor metabolism, and to discuss their clinical potential as biomarkers and therapeutic targets. Through mechanisms including miRNA sponging, protein interactions, regulation of mitochondrial dynamics, and modulation of metabolic enzymes, circRNAs influence key metabolic pathways by targeting glycolytic enzymes, lipid synthesis regulators, and glutaminolysis-related molecules to either facilitate or inhibit their expression. This review systematically summarizes the unique contributions of circRNAs to tumor metabolic reprogramming, highlighting key mechanisms such as regulation of peptide-encoding protein translation, mitochondrial localization function, gene promoter-targeted transcriptional regulation, and cross-pathway metabolic mediation, which underscore their distinct biological advantages and regulatory roles in tumor metabolism. The stability and tissue specificity of circRNAs make them promising diagnostic biomarkers, while their role in drug resistance mediated by metabolic reprogramming highlights their potential as therapeutic targets. Strategies such as circRNA inhibitors, mimics, and nanoparticle-based delivery systems are being explored to modulate tumor metabolism. Despite challenges including complex regulatory networks and limited manipulation tools, advances in high-throughput technologies and clinical trials hold promise for translating circRNA research into novel cancer therapies.

[This retracts the article DOI: 10.3727/096504016X14732772150541.].

Objective: To determine whether immunotherapy can bring new hope for patients with limited-stage small-cell lung cancer (LS-SCLC). We conducted this retrospective study to evaluate whether immunotherapy can achieve better efficacy in LS-SCLC patients.

Methods: We evaluated 122 LS-SCLC patients who received concurrent chemoradiotherapy (CCRT) or sequential chemoradiotherapy (SCRT) (Group A) and immunotherapy combined with CCRT/SCRT followed by immunotherapy (Group B), to assess the objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Factors affecting prognosis were also explored using Cox analysis. The prognosis of patients with type 2 diabetes and patients with different TNM stages was compared to guide the selection of clinical regimens.

Results: The overall ORR was 55.93%. The overall DCR was 98.31%. The DCR was 100% in Group A and 96.61% in Group B. There was no statistical difference in ORR and DCR. The overall median PFS was 9.86 months (95% CI, 8.62-11.10), and the difference in median PFS between the two groups was statistically significant (8.94 vs. 11.89 months, p = 0.03). The Cox regression analysis showed type 2 diabetes was associated with the survival prognosis. Patients with type 2 diabetes tended to choose immunotherapy combined with CCRT/SCRT. Patients in TNM stage IIIB had a significantly worse prognosis than those in stage I + II + IIIA.

Conclusion: We suggest that LS-SCLC patients who receive immunotherapy combined with CCRT/SCRT can achieve longer PFS than those with CCRT/SCRT. Type 2 diabetes and TNM stage affect the survival prognosis. Patients with type 2 diabetes may benefit from immunotherapy combination treatments.

Objectives: Cancer treatment relies heavily on accurate diagnosis and effective monitoring of the disease. These processes often involve invasive procedures, such as colonoscopy, to detect malignant tissues, followed by molecular analyses to determine relevant biomarkers. This study aimed to evaluate the clinical performance of droplet digital PCR (ddPCR) for detecting Kirsten Rat Sarcoma Viral Proto-Oncogene (KRAS), Neuroblastoma RAS Viral Oncogene Homolog (NRAS), and B-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) mutations in circulating tumor DNA (ctDNA) from colorectal cancer patients using liquid biopsy.

Methods: ctDNA was isolated from colorectal cancer (CRC) patients (n = 110) and analyzed for KRAS, BRAF, and NRAS mutations. The ctDNA obtained through liquid biopsy was analyzed using ddPCR, and the findings were compared with sequencing data from tumor DNA archived in formalin-fixed paraffin-embedded (FFPE) blocks.

Results: For KRAS mutations, ddPCR achieved a sensitivity of 72.0% and a specificity of 71.4%. However, when pooling all target mutations (KRAS, NRAS and BRAF), the overall sensitivity and specificity were lower, at 48.3% and 51.1%, respectively.

Conclusion: The results of this study indicate that the ddPCR analysis of ctDNA may provide complementary information for the molecular diagnosis of CRC patients.

Background: 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.

Methods: 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.

Results: 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.

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

Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

[This retracts the article DOI: 10.3727/096504016X14734149559061.].

Objectives: The current treatment options and therapeutic targets for triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer (BrCA), are limited. This study aimed to identify novel biomarkers and transcriptional regulatory networks (TRN) inherent in TNBC samples.

Methods: We analyzed pan-cancer BrCA datasets from The Cancer Genome Atlas (TCGA) to compare triple-positive breast cancer (TPBC) with TNBC. TRN algorithms and virtual inference of protein-enriched regulon (VIPER) were used to identify master regulators and their target genes. Utilizing TNBC cells (MDA-MB-231 and MDA-MB-468), we validated the relationship of nuclear factor erythroid 2-like 3 (NFE2L3) and basic helix-loop-helix family member E 40 (BHLHE40) by performing a luciferase assay. The expression levels of these targets were measured after transfections with plasmid and siRNA via qRT-PCR and western blots. The effect of these genes on cell proliferation and migration was studied using phenotypic assays.

Results: Using computational approaches, we identified NFE2L3 as a master regulator with BHLHE40 as its target gene. NFE2L3 protein binds to the promoter region of BHLHE40 and regulates its transcriptional activity. Additionally, silencing and overexpressing NFE2L3 and BHLHE40 in TNBC cell lines MDA-MB-231 and MDA-MB-468 showed that NFE2L3 directly regulates BHLHE40 at both transcriptional and translational levels. We found that BHLHE40 requires NFE2L3 for cell proliferation and migration in TNBC.

Conclusion: These findings underscore the significance of NFE2L3 and BHLHE40 in TNBC, highlighting NFE2L3's role in regulating the oncogenic activity of BHLHE40 in TNBC cells.