Oncology Research最新文献

Lung cancer is the most common but fatal malignant tumor worldwide. Patients with lung cancer experienced a relatively low 5-year overall survival rate, and issues such as metastasis and drug resistance remain prominent challenges in its clinical management. Neddylation, a novel type of post-translational modification, was overactivated in lung cancer and was closely associated with its occurrence, development, metastasis, and drug resistance. This review systematically summarizes the biological process of neddylation and deeply explores the latest research progress on how neddylation affects lung cancer cell proliferation, metastasis, and drug resistance mechanisms, with a focus on its regulation of key molecules such as Cullin-RING E3 ligases and the SCCRO family. Meanwhile, it concludes the current advances in potential therapeutic agents targeting neddylation-related targets, including small-molecule compounds (such as Pevonedistat) and natural extracts (such as arctigenin). Finally, the review prospectively evaluates the application potential and questions requiring further exploration of neddylation in lung cancer treatment. In conclusion, we aim to systematically summarize the biological process of neddylation, critically explore its roles in lung cancer proliferation, metastasis, and drug resistance, and evaluate the therapeutic potential of neddylation-targeting agents.

Background: 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.

Case description: 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.

Conclusions: 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.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Background: Photodynamic therapy (PDT) may eradicate residual malignant cells following sarcoma resection, through reactive oxygen species (ROS) mediated cytotoxicity, thus improve clinical outcomes. This study aims to assess the efficacy of 5-aminolevulinic acid (5-ALA) as a photosensitizer in combination with red light (RL) for PDT of bone sarcoma cells in vitro.

Methods: Three bone sarcoma cell lines underwent treatment with 5-ALA and RL or sham-RL (SL). 5-ALA uptake was assessed using flow cytometry. Production of ROS was measured using CellROX Green staining and fluorescence microscopy. Cell viability was assessed using Cell Counting Kit-8 assays.

Results: All cell lines showed significant 5-ALA uptake in comparison to the 0 mM control (p < 0.05). Production of ROS was significantly increased in cells treated with 5-ALA and RL, compared to those treated with RL and no 5-ALA or SL (p < 0.05). Viability was significantly reduced in cells treated with 5-ALA and RL, compared to SL (p < 0.05). At 72 h post-treatment, cell viability ranged from 6%-12% in 0.5 mM 5-ALA and RL-treated cells vs. 90%-137% in 0.5 mM 5-ALA and SL-treated cells.

Conclusion: 5-ALA-based PDT led to the desired increased production of ROS and reduction in cell viability in all cell lines. These preliminary in vitro results warrant further study with multicellular spheroid or animal models and suggest PDT has potential to be used as an adjuvant therapy to surgical resection in sarcoma management.

Colorectal cancer (CRC) is the third most common malignancy worldwide and the second leading cause of cancer-related deaths, accounting for approximately 10% of all cancer cases. By 2050, CRC incidence is expected to rise substantially, driven by population aging and greater exposure to risk factors in developing countries. Despite advances in medicine and pharmacy, the effectiveness of available treatments remains limited, underscoring the urgent need for innovative therapeutic strategies. This review summarizes and critically evaluates currently available CRC therapies and explores new emerging directions. Particular attention is given to the role of immunotherapy, targeted therapies, nanotechnology-based approaches, metal-based compounds, PROTAC technology, and personalized medicine, with emphasis on their efficacy, safety, accessibility, and mechanisms of drug resistance. In conclusion, surgery and chemotherapy remain the backbone of CRC treatment, but novel therapeutic approaches are reshaping the treatment landscape. Emerging strategies may offer improved patient tolerability and survival outcomes by reducing the occurrence of burdensome adverse effects. Persistent challenges such as drug toxicity, the emergence of resistance mechanisms, and inequalities in access to innovative therapies underscore the need for further translational research. Integrating personalized therapeutic approaches will also be crucial to achieving more effective, safer, and accessible treatment strategies for CRC.

Objectives: Early detection of hepatocellular carcinoma (HCC) is a significant challenge due to the limited sensitivity of alpha-fetoprotein (AFP). This study aimed to assess serum-derived extracellular vesicle-encapsulated GULP PTB domain-containing engulfment adaptor 1 (EV-GULP1) as a novel, noninvasive biomarker for HCC detection and prognosis, leveraging the potential of tumor-specific molecules carried by small extracellular vesicles (EVs).

Methods: The study utilized both internal and external cohorts of HCC patients and controls. Small EVs were isolated from serum samples, then characterized and validated to confirm their identity. The expression levels of EV-GULP1 were quantified using quantitative reverse transcription polymerase chain reaction (qRT-PCR).

Results: EV-GULP1 expression was found to be significantly higher in HCC patients, including those with early-stage disease, when compared to control groups. It demonstrated superior diagnostic accuracy over AFP, achieving an area under the curve (AUC) of 0.919, and was particularly effective in detecting AFP-negative cases. Furthermore, high EV-GULP1 expression correlated with worse overall and disease-free survival outcomes.

Conclusion: These findings highlight EV-GULP1 as a highly promising noninvasive biomarker for hepatocellular carcinoma. It offers improved diagnostic accuracy for early detection and better risk stratification for prognosis compared to the current standard, AFP.

Objectives: Although immune checkpoint inhibitors (ICIs) and targeted therapies have reshaped treatment non-small cell lung cancer (NSCLC) paradigms, prognosis remains poor for many patients due to delayed diagnosis and resistance mechanisms. Liquid biopsy offers a minimally invasive approach to monitoring tumor evolution. Among circulating biomarkers, circulating tumor cells (CTCs) and cancer-associated macrophage-like cells (CAM-Ls) may provide complementary prognostic insights. The study aimed to evaluate the prognostic role of CTC and CAM-Ls dynamic in metastatic NSCLC patients.

Methods: We retrospectively analyzed 77 patients with metastatic NSCLC who underwent CTC and CAM-L evaluation via the CellSearch® system at baseline (T0) and after three months of first-line treatment (T1) including chemotherapy, targeted therapy, or ICIs. Survival outcomes were analyzed using Kaplan-Meier and Cox regression analyses.

Results: Conversion to CTC-negative status at T1 was associated with improved outcomes, with median overall survival (OS) and progression-free survival (PFS) of 33 and 18 months, respectively, vs. 10 and 6 months in persistently positive patients (both p < 0.001). CTC negativity at T1 remained an independent prognostic factor for OS (HR: 6.68) and PFS (HR: 5.91, both p < 0.0001). CAM-L positivity at T1 also correlated with longer OS (30 vs. 12 months) and PFS (13 vs. 6 months, both p < 0.0001), particularly among ICI-treated patients. Combined CTC and CAM-L assessment further refined risk stratification.

Conclusions: Dynamic monitoring of CTCs and CAM-Ls provides actionable prognostic information in metastatic NSCLC. CTC-negative status predicted longer OS and PFS, while CAM-L positivity at T1 was associated with improved outcomes, particularly in ICI-treated patients. Combined assessment of both biomarkers may directly inform therapeutic decision-making, through early detection of outcomes.

Objectives: Gastric cancer (GC) remains a major global health concern, and Phosphoinositide-3-Kinase Regulatory Subunit 1 (PIK3R1), a regulatory subunit of the PI3K signaling pathway, may play a critical yet underexplored role in GC progression. This study aimed to investigate the prognostic significance of PIK3R1 in GC and its association with the tumor immune microenvironment.

Methods: PIK3R1 expression and its clinical relevance were analyzed using datasets from GC patients who underwent gastrectomy, including cohorts from The Cancer Genome Atlas (TCGA) and the Sun Yat-sen University Cancer Center (SYSUCC). Prognostic models integrating PIK3R1 expression with clinical parameters were constructed for both cohorts. The immune microenvironment associated with PIK3R1 expression was assessed through immunohistochemistry and single-cell RNA sequencing. In vitro assays were conducted to evaluate the effects of PIK3R1 on GC cell proliferation and migration.

Results: PIK3R1 was significantly overexpressed in GC tissues and was closely associated with aggressive tumor characteristics and poor clinical outcomes. A nomogram combining PIK3R1 expression with clinicopathological features effectively predicted patient prognosis. Knockdown of PIK3R1 in GC cells reduced proliferation and migration in vitro. Immunological profiling revealed that high PIK3R1 expression correlated with increased infiltration of forkhead box protein P3 (Foxp3⁺) and cluster of differentiation 73 (CD73⁺) T cells. Patients with low PIK3R1 expression and low CD73⁺ T cell infiltration had significantly better survival.

Conclusions: PIK3R1 overexpression is linked to poor prognosis in GC and influences the extent of immune cell infiltration within the tumor microenvironment. A novel prognostic model integrating PIK3R1 and CD73 expression with clinical parameters was established to stratify GC patients into distinct risk groups, offering potential value for personalized therapeutic strategies.

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.

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.