Epidemiological studies have spotlighted the intricate relationship between individual oral bacteria and tumor occurrence. Porphyromonas gingivalis and Fusobacteria nucleatum, which are known periodontal pathogens, have emerged as extensively studied participants with potential pathogenic abilities in carcinogenesis. However, the complex dynamics arising from interactions between these two pathogens were less addressed. This narrative review aims to summarize the current knowledge on the prevalence and mechanism implications of P. gingivalis and F. nucleatum in the carcinogenesis of oral squamous cell carcinoma (OSCC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC). In particular, it explores the clinical and experimental evidence on the interplay between P. gingivalis and F. nucleatum in affecting oral and gastrointestinal carcinogenesis. P. gingivalis and F. nucleatum, which are recognized as keystone or bridging bacteria, were identified in multiple clinical studies simultaneously. The prevalence of both bacteria species correlated with cancer development progression, emphasizing the potential impact of the collaboration. Regrettably, there was insufficient experimental evidence to demonstrate the synergistic function. We further propose a hypothesis to elucidate the underlying mechanisms, offering a promising avenue for future research in this dynamic and evolving field.

Background: Pancreatic cancer, specifically pancreatic ductal adenocarcinoma (PDAC), continues to pose a significant clinical and scientific challenge. The most significant finding of recent years is that PDAC tumours harbour their specific microbiome, which differs amongst tumour entities and is distinct from healthy tissue. This review aims to evaluate and summarise all PDAC studies that have used the next-generation technique, 16S rRNA gene amplicon sequencing within each bodily compartment. As well as establishing a causal relationship between PDAC and the microbiome. Materials and methods: This systematic review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. A comprehensive search strategy was designed, and 1727 studies were analysed. Results: In total, 38 studies were selected for qualitative analysis and summarised significant PDAC bacterial signatures. Despite the growing amount of data provided, we are not able to state a universal 16S rRNA gene microbial signature that can be used for PDAC screening. This is most certainly due to the heterogeneity of the presentation of results, lack of available datasets, and the intrinsic selection bias between studies. Conclusion: Several key studies have begun to shed light on causality and the influence the microbiome constituents and their produced metabolites could play in tumorigenesis and influencing outcomes. The challenge in this field is to shape the available microbial data into targetable signatures. Making sequenced data readily available is critical, coupled with the coordinated standardisation of data and the need for consensus guidelines in studies investigating the microbiome in PDAC.

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related death. Although molecular stratification and multimodal therapy have improved outcomes in selected patients, overall prognosis is still limited by late diagnosis, heterogeneity, and treatment resistance. Immune checkpoint inhibitors (ICIs) have substantially improved survival outcomes in a subset of patients; however, the overall benefit remains limited, and both primary and acquired resistance are common. Neutrophils, as key effectors of innate immune responses, can be activated by diverse stimuli and release neutrophil extracellular traps (NETs). Growing evidence indicates that neutrophils and NETs contribute to remodeling of the tumor microenvironment (TME) in NSCLC, promoting resistance to ICIs. This review systematically summarizes the biological features, key molecular pathways, and inducing factors of neutrophils and NETs in lung cancer and synthesizes evidence supporting their roles as biomarkers of ICI efficacy and prognosis. We further focus on the mechanisms by which NETs mediate immunosuppression and foster an immune-excluded TME, thereby driving resistance to immunotherapy. In addition, we outline potential therapeutic and combination strategies targeting neutrophils and NETs, providing a theoretical basis for developing optimized immunotherapy approaches for NSCLC that target neutrophils and NETs.

In pancreatic ductal adenocarcinoma (PDAC), clinicians often ask whether young age is associated with more aggressive disease or patients more likely to tolerate curative-intent multimodality treatment. The prognostic meaning of age after surgery remains uncertain. We analyzed a retrospective multicenter surgical cohort of patients with resected non-metastatic PDAC. Candidate clinical variables were evaluated in univariable Cox models. The prespecified primary multivariable model included age, sex, N status, T stage, and CA19-9 status. Adjuvant therapy was evaluated in a sensitivity model. The cohort included 696 surgical patients; 70 (10.1%) were aged < 55 years. Median overall survival was 34.4 months in patients aged < 55 years versus 22.0 months in those aged ≥ 55 years (log-rank p = 0.019). In the primary multivariable model, age < 55 years remained independently favorable (HR 0.66, 95% CI 0.49–0.89; p = 0.007). Elevated CA19-9 value independently predicted worse survival (HR 1.39, 95% CI 1.13–1.71; p = 0.002). The sensitivity model confirmed favorable associations for young age and not elevated CA19-9 value. In surgically managed PDAC patients, young age and normal CA19-9 value carried independent favorable prognostic information. Prognosis was also shaped by nodal status, T stage, and receipt of adjuvant therapy.

Nerve growth factor (NGF) signaling is involved in pancreatic ductal adenocarcinoma (PDAC) neurotropism, perineural invasion, pain, and tumor-stromal crosstalk, but its value as a circulating biomarker remains poorly defined. We retrospectively analyzed 51 patients with PDAC who underwent serial liquid-biopsy assessment across perioperative and advanced-disease timepoints. Circulating β-NGF was assessed in plasma, and samples without measurable NGF were classified as non-detectable. NGF was analyzed as both a zero-inflated continuous variable and a binary detectable/non-detectable biomarker. Phase-aligned associations with recurrence, disease-free survival, first-line progression-free survival, CA19-9, CEA, TGFβ, PD-L1, pain, and pathological perineural invasion were evaluated using non-parametric and permutation-based methods with false-discovery-rate adjustment. NGF availability was highest at first-line treatment initiation, where 9 of 40 patients had detectable NGF (22.5%). The clearest signal emerged postoperatively: patients who subsequently recurred had higher NGF values than those who did not (median 25.5 pg/mL vs. non-detectable; nominal p = 0.038). Detectable postoperative NGF was directionally associated with recurrence, while detectable NGF at first-line treatment initiation was associated with numerically shorter progression-free survival. Pooled active-disease measurements did not show a clear NGF increase versus postoperative samples, arguing against a generic disease-burden signal. No association remained significant after false-discovery-rate correction; therefore, all observed signals should be interpreted as exploratory and hypothesis-generating. These findings support prospective validation of circulating NGF within multimarker liquid-biopsy strategies focused on postoperative recurrence, perineural invasion-related biology, and treatment resistance in PDAC.