Fusobacterium nucleatum (Fn) has been increasingly recognized as a crucial mediator of colorectal cancer (CRC) biology, particularly in microsatellite-stable (MSS) tumors, where immune checkpoint inhibitors (ICIs) have shown limited efficacy. Rather than representing a passive microbial passenger, Fn actively shapes tumor behavior by adhering to epithelial cells, activating oncogenic signaling, and promoting epithelial–mesenchymal transition (EMT). At the same time, it remodels the tumor microenvironment, driving immune suppression through inhibitory receptor engagement, accumulation of myeloid-derived cells, and metabolic reprogramming of tumor-associated macrophages. These mechanisms converge to impair cytotoxic immunity and contribute to both intrinsic and acquired resistance to ICIs. Beyond immune escape, Fn interferes with conventional chemotherapy by sustaining autophagy and blocking ferroptosis, thereby linking microbial colonization to multidrug resistance. Most of these mechanisms derive from preclinical in vitro and in vivo models, where causal relationships can be inferred. In contrast, human data are mainly observational and provide correlative evidence without proving causality. No interventional clinical studies directly targeting Fn have yet been conducted. Its enrichment across the adenoma–carcinoma sequence and consistent detection in both tumor and fecal samples highlight its potential as a biomarker for early detection and patient stratification. Importantly, multidimensional stool assays that integrate microbial, genetic, and epigenetic markers are emerging as promising non-invasive tools for CRC screening. Therapeutic strategies targeting Fn are also under exploration, ranging from antibiotics and bacteriophages to multifunctional nanodrugs, dietary modulation, and natural microbiota-derived products. These approaches may not only reduce microbial burden but also restore immune competence and enhance the efficacy of immunotherapy in MSS CRC. Altogether, current evidence positions Fn at the intersection of microbial dysbiosis, tumor progression, and therapy resistance. A deeper understanding of its pathogenic role may support the integration of microbial profiling into precision oncology frameworks, paving the way for innovative diagnostic and therapeutic strategies in CRC.

The introduction of novel oncologic therapies, including targeted agents, immunotherapies, and antibody–drug conjugates, has transformed the therapeutic landscape of cancer care. This evolution has resulted in a dual clinical scenario; while survival outcomes have markedly improved, leading to a growing population of long-term cancer survivors, an increasing incidence of previously unrecognized treatment-related toxicities has emerged. Among these, cardiovascular adverse events represent some of the most prevalent and clinically significant complications observed in both conventional chemotherapy and modern therapeutic regimens. Cardiotoxicity has become a major concern, with the potential to adversely affect not only cardiovascular health but also the continuity and efficacy of oncologic treatments, thereby impacting overall survival. This opinion paper synthesizes current evidence, identifies critical gaps in knowledge, and advocates for a multidisciplinary, evidence-based framework to guide the prevention, early detection, and optimal management of cardiotoxicity associated with anticancer therapies.

Background: Fusobacterium nucleatum is a pathobiont that plays a dual role as both a commensal and a pathogen. The oral cavity typically harbors this anaerobic, Gram-negative bacterium. At the same time, it is closely linked to colorectal cancer due to its potential involvement in tumor progression and resistance to chemotherapy. The mechanism by which it transforms from a commensal to a pathogen remains unknown. For this reason, we investigated the role of oxidative status as an initiatory factor in changing the bacterium’s pathogenicity profile. Methods: A clinical strain of F. nucleatum subsp. animalis biofilm was exposed to different oxidative stress levels through varying subinhibitory amounts of H₂O₂. Subsequently, we investigated the bacterium’s behavior in vitro by infecting the HT-29 cell line. We evaluated bacterial colonization, volatile sulfur compounds production, and the infected cell’s oxidative status by analyzing HMOX1, pri-miRNA 155, and 146a gene expression. Results: The bacterial colonization rate, dimethyl sulfide production, and pri-miRNA 155 levels all increased when stressed bacteria were used, suggesting a predominant pathogenic function of these strains. Conclusions: The response of F. nucleatum to different oxidative conditions could potentially explain the increase in its pathogenic traits and the existence of environmental factors that may trigger the bacterium’s pathogenicity and virulence.

Urothelial carcinoma predominantly affects older patients, who often exhibit frailty, comorbidities, renal impairment, and reduced physiological reserve. We evaluated overall survival (OS) and progression-free survival (PFS) with first-line immune-based strategies in patients aged ≥65 years with advanced or metastatic urothelial carcinoma. The aim was to characterize treatment effects within this age-defined subgroup, not to determine whether age modifies treatment efficacy compared with younger patients. Methods: We conducted a systematic review and meta-analysis of phase 3 randomized trials published from January 2015 to May 2026 reporting age-specific survival outcomes. Combination regimens were compared with platinum-based chemotherapy using random-effects models. Results: Combination strategies improved OS versus chemotherapy (HR 0.79, 95% CI 0.64–0.96), although heterogeneity was substantial (I² = 69.7%) and the prediction interval crossed the null (0.48–1.27). Class-specific HRs were 0.56 (95% CI 0.26–1.20) for ADC plus ICI, 0.85 (0.77–0.95) for ICI plus chemotherapy, and 0.91 (0.34–2.42) for dual-checkpoint inhibition. PFS favoured experimental treatment but remained imprecise (HR 0.54, 95% CI 0.27–1.08; I² = 89.5%). Excluding ADC plus ICI trials attenuated the OS effect (HR 0.88, 95% CI 0.80–0.96), indicating that the pooled estimate was influenced by these trials. ICI monotherapy did not improve OS. Conclusions: First-line immune-based combinations improved survival in selected patients aged ≥65 years, but benefit varied across treatment classes and should not be considered uniform across regimens. These findings do not establish whether age modifies treatment efficacy. Age-specific safety data were insufficient to define the benefit–risk profile of individual strategies.

INPLASY202560030 Environmental Endocrine Disruptors and Endometrial Cancer Risk: A Comprehensive Systematic Review Keywords: endometrial cancer; endocrine disruptors chemicals; BPA; cadmium; phthal…