Oncology Research最新文献

Background: Glioblastoma (GBM) remains the most aggressive primary brain tumour in adults, marked by pronounced cellular heterogeneity, diffuse infiltration, and resistance to conventional treatment. In recent years, transcriptomic profiling has provided valuable insights into the molecular mechanisms that govern the progression of glioblastoma. This systematic review aims to synthesise the current literature on dysregulated gene expression in GBM, focusing on gene signatures associated with stemness, immune modulation, extracellular matrix remodelling, metabolic adaptation, and therapeutic resistance.

Methods: We conducted a systematic search of PubMed, The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and the GlioVis portal for studies published between January 2005 and April 2025, limited to English-language reports. Studies were eligible if they included adult glioblastoma tissue or patient-derived datasets and reported gene-level expression or clinical associations. Reviews, commentaries, and studies on non-GBM gliomas were excluded. Screening followed the PRISMA 2020 checklist, with 410 records initially identified, 90 duplicates removed, and 125 studies retained after full-text review. Data were synthesised descriptively, and findings were validated against TCGA/CGGA expression datasets to ensure consistency across cohorts.

Results: We categorised recurrently dysregulated genes by their biological function, including transcription factors (SOX2, ZEB2), growth factor receptors (EGFR, PDGFRA), immune-related markers (PD-L1, TAP1, B2M), extracellular matrix regulators (MMP2, LAMC1, HAS2), and metabolic genes (SLC7A11, PRMT5, NRF2). For each group, we examine the functional consequences of transcriptional alterations and their role in driving key glioblastoma phenotypes, including angiogenesis, immunosuppression, invasiveness, and recurrence.

Conclusion: We further discuss the prognostic implications of these gene signatures and evaluate their potential utility in precision medicine, including current clinical trials that target molecular pathways identified through transcriptomic data. This review highlights the power of gene expression profiling to stratify glioblastoma subtypes and improve personalised therapeutic strategies.

Objectives: Triple-negative breast cancer (TNBC) is the breast cancer subtype with the poorest prognosis. This study aimed to elucidate the molecular pathways through which isoliquiritigenin (ISL), a natural chalcone compound derived from licorice and other plant roots, targets interferon regulatory factor 5 (IRF5) in TNBC.

Methods: TNBC cell lines were cultured and subjected to IRF5 knockdown using short hairpin RNA. Cell proliferation was assessed by cell counting kit-8 (CCK-8) assay and colony formation assays. Western blotting and quantitative reverse transcription polymerase chain reaction (RT-PCR) were employed to measure expression levels of IRF5, solute carrier family 7 member 5 (SLC7A5), and indoleamine 2,3-dioxygenase 1 (IDO1). Intracellular tryptophan and its metabolites were quantified using commercially available assay kits and high-performance liquid chromatography (HPLC). TNBC cells were treated with various concentrations of ISL to evaluate its effects on proliferation and tryptophan metabolism.

Results: IRF5 was highly expressed in TNBC cell lines. Silencing IRF5 significantly inhibited cellular proliferation and growth. Knockdown of IRF5 reduced the expression of SLC7A5 and IDO1, leading to decreased intracellular levels of tryptophan and its metabolites. ISL markedly suppressed TNBC cell proliferation and disrupted tryptophan metabolism in tumor cells.

Conclusion: ISL may inhibit TNBC progression by downregulating IRF5 and interfering with SLC7A5/IDO1-mediated tryptophan metabolic reprogramming, suggesting a potential therapeutic mechanism for TNBC treatment.

Background: Motif interacting with ubiquitin-containing novel DUB family-1 (MINDY1) could enhance the stability of programmed death-ligand 1 (PD-L1). The study aimed to investigate whether MINDY1 regulates the immune escape of hepatocellular carcinoma (HCC) mediated by PD-L1.

Methods: MINDY1 and PD-L1 levels were detected through Western blot. The link between MINDY1 and PD-L1 was validated using the co-immunoprecipitation assay. The malignant biology of HCC cells was assessed through Cell Counting Kit-8, Carboxyfluorescein Succinimidyl Ester staining, transwell, and wound healing assay. CD8⁺ T cells were isolated and then co-cultured with HCC cells. Enzyme-linked immunosorbent Assay kits detected CD8⁺ T cytokine content. CD8⁺ T cell activation markers, PD-L1 ubiquitination levels, and Wnt/β-catenin pathway-associated protein levels were detected through Western blot. A HCC nude mouse model was developed, Ki-67 positivity and CD8⁺ T-cell infiltration were assessed through pathological staining and flow cytometry.

Results: MINDY1 and PD-L1 levels were elevated in HCC. Overexpression of MINDY1 increased migrating and invading cells, elevated cell viability, and decreased apoptosis in HCC cells, leading to PD-L1 deubiquitination. Knockdown of MINDY1 reversed all of these indicators. Co-culturing with HCC cells overexpressing MINDY1 resulted in decreased proliferative capacity and cytotoxicity of CD8⁺ T cells, increased apoptosis, and decreased levels of cytokines and activation markers in CD8⁺ T cells. MINDY1 triggered Wnt/β-catenin pathway, Wnt activators further promoted PD-L1 deubiquitination and suppressed CD8⁺ T cell activation. MINDY1 overexpression increased PD-L1 and Ki67 positivity level in HCC tumors, suppressed CD8⁺ T-cell infiltration.

Conclusion: MINDY1 promotes PD-L1 deubiquitination and inhibits CD8⁺ T cell activation by stimulating the Wnt/β-catenin pathway, consequently promoting HCC tumor immune escape.

This review aims to explore the development, challenges, and future directions of UCAR cell therapy as a scalable alternative to autologous CAR-T for cancer treatment. Consequently, limitations of autologous CAR-T, including long production, variable quality, and cost, drive off-the-shelf UCAR development to standardize manufacturing and improve access. Current UCAR-T cell strategies focus on mitigating the risks of graft-vs.-host disease and host-vs.-graft rejection through advanced gene editing technologies, including clustered regularly interspaced short palindromic repeat-associated system Cas9-mediated knockout of the T cell receptor, human leukocyte antigen, and cluster of differentiation 52 (CD52). Beyond conventional T cells, cell types such as double-negative T cells, γδT cells, and virus-specific T cells are being engineered with CARs to improve tumor targeting and minimize off-tumor toxicity. UCAR-T therapy is frequently used for hematologic malignancies, including acute lymphoblastic leukemia, non-Hodgkin lymphoma, and multiple myeloma, with efficacy and safety supported by numerous clinical studies. Although trials for solid tumors (e.g., CYAD-101, CTX130) show modest responses, challenges such as tumor heterogeneity and T cell exhaustion remain. Future research should focus on optimizing gene editing precision, integrating combination therapies, and advancing scalable manufacturing platforms. With expanded targets and cell types, UCAR therapies show promise for both hematologic and solid tumors, reshaping cancer treatment and patient outcomes.

Objective: The tumor microenvironment plays a pivotal role in prostate cancer progression and may differ across metastatic sites. This study aimed to evaluate and compare the primary and metastatic prostate adenocarcinoma tumor microenvironment.

Methods: A total of 27 formalin-fixed paraffin-embedded tissue samples derived from 17 patients diagnosed with prostate adenocarcinoma, including the primary tumors, and the corresponding metastatic lymphatic and hematogenous lesions from various anatomical sites. Immunohistochemical labeling was performed using antibodies against Cluster of Differentiation 3 epsilon chain (CD3e), CD8 alpha chain (CD8a), Cluster of Differentiation 68 (CD68), Cluster of Differentiation 163 (CD163), Forkhead box P3 (FOXP3), Cytotoxic T-Lymphocyte-Associated protein 4 (CTLA-4), B7 homolog 3 (B7-H3), Programmed cell death protein 1 (PD-1), and Marker of proliferation Ki-67 (Ki-67). Comparisons were made between primary and metastatic tumors to assess differences in immune cell infiltration, checkpoint expression, and proliferative indices.

Results: Samples were classified into three groups: Primary Tumor n = 12, Lymphatic Metastasis n = 7, and Hematogenous Metastasis n = 10. FOXP3 (p = 0.0017) and CD163 (p = 0.0316) expression levels were significantly higher in the Hematogenous Metastasis compared to both the Primary Tumor and Lymphatic Metastasis. PD-1 showed a clear trend (p = 0.0577) toward higher levels in the Primary Tumor compared to both the Hematogenous Metastasis and Lymphatic Metastasis groups, suggesting distinct immunological landscapes depending on tumor location and progression.

Conclusion: Diverse PD-1, CD163, and FOXP3 profiles were observed in primary and metastatic microenvironments of prostate cancer. These findings may contribute to the development of personalized therapeutic strategies and novel prognostic tools beyond conventional histological and TNM staging.

Cluster of differentiation 47 (CD47), an immune checkpoint commonly referred to as the "don't eat me" signal, plays a pivotal role in tumor immune evasion by inhibiting phagocytosis through interaction with signal regulatory protein alpha (SIRPα) on macrophages and dendritic cells (DCs). Although early enthusiasm drove broad clinical development, recent discontinuations of major CD47-targeted programs have prompted re-evaluation of its therapeutic potential. The purpose of this commentary is to contextualize the setbacks observed with first-generation CD47 inhibitors and to highlight strategies aimed at overcoming their limitations. Clinical challenges, including anemia, thrombocytopenia, suboptimal pharmacokinetics, and limited single-agent efficacy, underscore the need to develop safer, more selective approaches. Emerging next-generation strategies, such as SIRPα-directed agents, bispecific antibodies, and conditionally active therapeutics, are designed to enhance safety and tumor selectivity and reduce systemic toxicity. In addition, spatial profiling and biomarker-driven patient selection are advancing toward guiding rational therapeutic combinations, including with "eat-me" signals (e.g., calreticulin [CALR]) or DNA damage response therapies (e.g., poly(ADP-ribose) polymerase [PARP] inhibitors). Rather than signaling failure, these developments underscore the need for precision, context-specific applications, and adaptive trial designs to realize the durable therapeutic promise of CD47 blockade in cancer immunotherapy.

Gastric Cancer (GC) is a highly prevalent and poorly prognostic gastrointestinal malignancy with low overall treatment efficacy worldwide. Early diagnostic markers and potential therapeutic targets for GC treatment are urgently needed. UFMylation, a novel ubiquitin-like modification is indispensable for numerous fundamental cellular processes. Deficiency in this modification is reported to be associated with several human diseases including cancer. Accumulating evidence suggests that the expression of the key UFMylation components is closely associated with GC cell proliferation, invasion, metastasis, and chemotherapy resistance. Recent clinical studies have further highlighted the prognostic value and therapeutic potential of UFMylation in the clinical management of GC. However, the precise molecular mechanisms through which UFMylation contributes to GC remain largely unclear. This review aims to summarize recent findings on the functional roles of UFMylation in diverse cellular processes, such as endoplasmic reticulum (ER) homeostasis, DNA damage response (DDR), protein translation, and quality control pathways, discuss potential underlying mechanisms in GC development and progression, and to explore potential therapeutic implications targeting the UFMylation pathway in GC.

Pancreatic cancer (PC) is an extremely aggressive cancer of the digestive system with insidious onset and the lack of effective biomarkers, resulting in late-stage diagnosis and poor prognosis. Exosomal non-coding RNAs (ncRNAs) are key mediators of intercellular communication that drive PC initiation and advancement. By modulating gene expression, they impact tumor microenvironment (TME) remodeling, proliferation, migration, apoptosis, and immune evasion. Critically, exosomal ncRNAs serve as promising biomarkers for early diagnosis and prognostic assessment. This review summarizes the current research achievements regarding exosomal ncRNAs in PC, systematically elaborating on their roles in tumor occurrence, metastasis, chemoresistance and the TME. Furthermore, by integrating the potential of exosomal ncRNAs in the diagnosis, treatment and prognosis of PC and by highlighting the challenges and future directions, this review aims to offer novel insights for future research and clinical translation of exosomal ncRNAs in PC.

Objectives: Monitoring of Cancer Antigen 125 (CA125) during ovarian cancer (OC) maintenance treatment with poly(ADP-ribose) polymerase inhibitors (PARPis) may be insufficient when using Gynecologic Cancer Intergroup (GCIG) biochemical progression criteria. This study aimed to evaluate the usefulness of CA125 monitoring in detecting OC recurrence during PARPis maintenance treatment.

Methods: This multicenter retrospective cohort study included patients with primary OC who achieved complete or partial response after first-line platinum-based chemotherapy followed by PARPis maintenance treatment. Progression was defined using Response Evaluation Criteria in Solid Tumors (RECIST) and GCIG biochemical criteria. New biochemical progression definitions, based on CA125 nadir determined using receiver operating characteristic (ROC) curve analysis, were proposed. Concordance between radiological and biochemical progression was assessed.

Results: Of 142 patients, progression was detected in 54 (38.03%) and 29 (20.42%) using RECIST and GCIG criteria, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the GCIG criteria were 53.70% [95% confidence interval (CI): 39.61%-67.38%], 100.00% [95% CI:95.91%-100.00%], 100.00% [95%CI: 88.10%-100.00%] and 77.88% [95% CI: 72.54%-82.43%], respectively. A cut-off of 1.59× nadir achieved 88.90% sensitivity and 87.20% specificity [Area Under Curve (AUC): 91.10%, 95% CI: 84.70%-97.40%] with a false positive rate (FPR) of 12.67%. Defining biochemical progression as an increase in CA125 of ≥3× nadir achieved sensitivity, specificity, PPV, NPV, and FPR of 79.63% [95% CI: 66.47%-89.37%], 98.86% [95% CI: 93.83%-99.97%], 97.73% [95% CI: 85.91%-99.67%], 88.78% [95% CI: 82.35%-93.06%], and 1.14%, respectively. Diagnostic accuracy was higher using the ≥3× nadir criterion compared with GCIG definition (91.55% vs. 82.39%).

Conclusion: GCIG biochemical progression criteria during PARPis maintenance treatment after first-line chemotherapy missed 46.3% of progressing patients. A new criterion-CA125 ≥3× nadir-improves sensitivity and NPV, while maintaining high specificity, offering a simple and practical approach for clinical implementation.

Lactylation, a post-translational modification process that adds lactate groups to lysine residues, plays a crucial role in cancer biology, especially in drug resistance. However, the specific molecular mechanisms of lactylation in cancer progression and drug resistance are still unclear, and therapeutic strategies targeting the lactylation pathway are expected to overcome metabolic reprogramming and immune evasion. Therefore, this article provides a comprehensive description and summary of lactylation modification and tumor drug resistance. Numerous studies have shown that, due to the Warburg effect, there is an abnormally high level of lactate in tumor cells. Elevated levels of lactate promote metabolic reprogramming and alter key cellular processes, including gene expression, DNA repair, and immune regulation. These cellular processes are precisely the key factors for tumor cells to develop drug resistance. Lactylation also affects the tumor microenvironment, promoting immune evasion and resistance to immunotherapy in tumor cells. This modification affects proteins involved in metabolic pathways, glycolysis, and mitochondrial function, further supporting tumor growth and metastasis. Therefore, this article provides a comprehensive description and summary of lactylation modification and tumor drug resistance to clarify the specific mechanisms between the two and provide references and directions for future research on tumor drug resistance.