The gastrointestinal tract contains a dense multi-kingdom ecosystem in which bacteria, fungi, archaea, viruses, the mucosa, and the immune system interact. Although cancer microbiome research has focused mainly on bacteria, the gut virome dominated by bacteriophages may influence gastrointestinal carcinogenesis by reshaping bacterial communities, transferring functional genes, modulating inflammation, and altering treatment response. The strongest evidence comes from colorectal cancer, where multiple cohorts show altered phage diversity, temperate-phage enrichment, disrupted phage–bacteria networks, and reproducible stool-based diagnostic signals. Emerging studies in pancreatic cancer, esophageal adenocarcinoma, hepatocellular carcinoma, and precursor lesions suggest that virome disruption extends beyond colorectal cancer, although evidence remains uneven. Classic oncogenic viruses, including Epstein–Barr virus and hepatitis viruses, provide complementary examples of direct viral carcinogenesis in digestive organs. Anelloviruses are widespread in healthy individuals and are not established causes of cancer, but their abundance and composition may reflect immune status, inflammation, tissue injury, and altered host viral ecology. Virome-related interventions remain clinically immature: fecal microbiota transplantation has reached small phase I/II studies in gastrointestinal cancers, whereas phage, fecal-filtrate, and fecal virome approaches remain preclinical or non-oncology; direct oncolytic viruses have reached late-phase testing. Major barriers include viral dark matter, specimen and assay heterogeneity, disease-related confounding, limited external validation, and weak causal evidence. Standardized, mechanistically anchored, multi-kingdom studies are needed to establish clinical utility.

Messenger RNA vaccines have moved rapidly from the infectious-disease area into oncology. They now represent an attractive therapeutic option for gastrointestinal (GI) cancers. Personalised constructs, designed to elicit tumour-specific T-cell immunity, have shown acceptable safety and clear immunogenicity in early-phase trials of colorectal and pancreatic cancers. These early signals are encouraging, but several obstacles still exist for routine clinical use: tumour heterogeneity, immune evasion, the difficulty of selecting the right target antigens, and the stability of the delivery platform itself. The possibility of a combination with immune checkpoint inhibitors is currently being explored to deepen and prolong responses, although the durability of benefit remains to be established. In this review, we outline the current landscape of mRNA vaccine development for GI malignancies, with particular attention to delivery strategies and multimodal immunotherapy. Finally, we discuss the directions most likely to help move these agents from the laboratory into everyday clinical practice.

Background: Melanoma disproportionately affects older adults, who account for a growing share of cases as populations age. Its incidence rises with age, and the number of ultra-octogenarians (≥85 years) is expected to triple by 2050, particularly in high-incidence regions such as Australia, North America and Europe. Moreover, older adults frequently present with substantial comorbidities, making management complex and complicating treatment decisions. Methods: This comprehensive review summarizes evidence concerning the clinicopathological characteristics, treatment patterns, systemic therapy outcomes, and geriatric considerations relevant to patients aged 75 years or older with melanoma. PubMed/MEDLINE was searched from January 2000 to March 2026. Reference lists of eligible articles and relevant reviews were examined to identify additional studies. Priority was given to studies reporting age-stratified outcomes for patients aged at least 75 years. Because relatively few studies reported outcomes specifically for patients aged ≥75 years, evidence using thresholds of ≥65, ≥70, or ≥80 years was included when directly relevant. Age thresholds are reported for each study and should not be considered interchangeable. Results: Most evidence specific to patients aged ≥75 years derives from retrospective cohorts and registries. Compared with younger patients, elderly patients more often present with melanomas of the head, neck, hands and feet, a higher prevalence of the nodular subtype, greater Breslow thickness, higher mitotic rates and lower tumor-infiltrating lymphocyte density. Diagnosis is frequently delayed due to difficulties with self-examination, visual impairment, benign age-related skin changes and social factors. Despite presenting such a high-risk disease, older patients are less likely than their younger counterparts to receive immunotherapy or BRAF/MEK-targeted agents. This treatment gap may reflect comorbidities, altered pharmacokinetics, concerns about toxicity, under-representation in pivotal trials, and limited caregiver support. Available real-world data suggest that the efficacy of immune checkpoint inhibitors and targeted therapies is comparable to that in younger adults, although treatment selection, discontinuation, hospitalization, and dose modification differ across studies. Conclusions: Melanoma in older adults has distinct clinical and pathological patterns, but treatment evidence for patients aged ≥75 years remains limited and subjected to selection bias. Tailored, geriatric-informed treatment strategies integrating tumor biology, comorbidity, functional status and patient preferences are needed to optimize outcomes for patients aged 75 years and older.

Background/Objectives: Standard guidelines for treating locally advanced and metastatic gastroesophageal cancer (GEC) involve combination regimens of chemotherapy and immunotherapy. Patient eligibility for these treatments is primarily guided by the programmed cell death ligand 1 (PD-L1) combined positive score (CPS). This approach assumes that a single baseline biopsy accurately reflects a stable, tumor-wide PD-L1 status, an assumption increasingly challenged by spatial and temporal heterogeneity. This systematic review aims to synthesize existing data on PD-L1 expression dynamics before and after systemic therapy in GEC, and to evaluate whether these changes differ between neoadjuvant and metastatic settings. Methods: We systematically searched PubMed/MEDLINE (up to May 2026) for studies reporting paired pre- and post-treatment PD-L1 status in gastric and gastroesophageal junction cancers. This systematic review was conducted in accordance with the PRISMA 2020 guidelines. Narrative synthesis and qualitative data transformation were structured following the Synthesis Without Meta-analysis (SWiM) reporting framework. Study-level risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). Results: Eleven studies were included in this systematic review, stratified into neoadjuvant (n = 6) and metastatic (n = 5) settings. Our findings suggest that changes in PD-L1 expression in gastroesophageal cancer depend heavily on the clinical setting. Specifically, an upward trend in post-treatment PD-L1 expression was evident in the neoadjuvant setting, with 5 of 6 studies reporting a prevalence of PD-L1 gain ranging from 6.3% to 33.3%. Conversely, PD-L1 downregulation was consistently reported across all metastatic studies, with loss rates ranging from 19.3% to 44.4%. Conclusions: PD-L1 status in gastroesophageal cancer changes dynamically after treatment. These findings highlight the limitations of relying on archival tissue and support the use of repeat biopsies to track evolving tumor phenotypes. This study is primarily limited by small sample sizes of paired biopsies, technical heterogeneity in PD-L1 scoring and treatment regimens, potential publication bias, and the lack of prospective registration.