Centre de Recherche des Cordeliers

Chronic kidney disease and its most severe complication, end-stage renal disease (ESRD), represents an estimated financial burden of €4.4billion in 2021 in France. Therapeutic patient education (TPE) improves ESRD management and health outcomes. This study explored whether providing access to an interactive web-based TPE platform with community features was cost-effective. A within-trial cost-utility analysis was carried out over an 18 months horizon, using data from the PIC-R (Plateforme Interactive Communautaire-dialyse et transplantation Rénale) trial. ESRD or post-transplant patients were randomized 1:1:1 to a control group with no specific TPE program (Control), an intervention group with online TPE (e-TPE) and an intervention group with online TPE coupled with community features such as a patient forum and a chatroom with both patients and health care professionals (e-TPE + chat). The outcome measure was the cost per quality-adjusted life-year (QALY) and per year of full capability (YFC). Both intention-to-treat (ITT) and per protocol (PP) analyses were conducted, and missing data were handled using multiple imputation and selection models. Sensitivity analyses were performed. Among the 815 patients assessed for eligibility across 12 French centres, a total of 549 patients were included in the economic analysis: 186 in the Control group, 189 in the e-TPE group and 174 in the e-TPE + chat group. The e-TPE group demonstrated cost savings and slightly higher QALYs compared to the control group, making e-TPE dominant. Conversely, the e-TPE + chat intervention resulted in higher costs without substantial effectiveness gains, making it not cost-effective. e-TPE was deemed cost-effective for ESRD patients, while e-TPE + chat was not. Web-based platforms improve ESRD management when targeted to likely users.

Overexpression of complement genes in the tumor microenvironment, including Factor H (FH), is a strong predictor of poor prognosis in multiple cancers. Its canonical functions in the bloodborne complement cascade, though, cannot explain this prognostic impact. Here, we demonstrate that FH operates within the intracellular space in fibroblasts and tumor cells. By transcriptomics approach in patient tumors, cellular and biochemical assays we revealed that the prognostic impact of FH overexpression is mediated mainly by its cell-intrinsic functions in tumor-promoting fibroblasts and malignant cells. Intranuclear FH interacts with the cell cycle-transcription factor E2F3. FH also promotes proliferation by lowering the nuclear p53 pool. Moreover, in ccRCC cancer cells, FH also regulates cytoskeleton organization and cell morphology, potentially, via interaction with the actin capping CapZ complex. Therefore, complement FH acts as a multitasking effector, regulating cell cycle and actin polymerization, challenging the paradigm of extracellular space-restricted functioning, considered for many complement proteins.

Urothelial bladder cancer (UBC) carries significant mortality and treatment morbidity. Conventional diagnostic and monitoring methods, including cystoscopy and biopsy, are invasive and limited in sensitivity. Circulating tumor DNA (ctDNA), a minimally-invasive "liquid biopsy," has emerged as a promising tool for real-time disease assessment. This study aimed to systematically evaluate the diagnostic, prognostic, and predictive value of plasma and urine ctDNA in localized, locally advanced, and metastatic UBC. A systematic review was conducted according to PRISMA guidelines using PubMed, MEDLINE, and Web of Science databases (January 2016-October 2025). Eligible studies evaluated plasma and urine ctDNA. Main outcomes included diagnostic performance, correlation with tissue mutations, disease monitoring, and prognostic or predictive value. Data synthesis focused on ctDNA detection methods, timing relative to treatment, and survival outcomes. KEY FINDINGS AND LIMITATIONS: ctDNA showed strong concordance with tumor tissue mutations and high potential for real-time monitoring of tumor burden. Data are more robust in muscle-invasive bladder cancer (MIBC) than non-muscle-invasive bladder cancer (NMIBC). Postcystectomy ctDNA positivity was an independent predictor of recurrence-free, progression-free, and overall survival. ctDNA clearance correlated with response to neoadjuvant chemotherapy and immune checkpoint inhibitors. In metastatic disease, high ctDNA mutation burden was associated with shorter overall survival and resistance mechanisms, such as PIK3CA-mediated fibroblast growth factor receptor inhibitor resistance. Limitations included heterogeneous methodologies, variable assay sensitivity, and small patient cohorts. ctDNA represents a powerful non-invasive biomarker for diagnosis, surveillance, and treatment guidance in UBC. Ongoing phase III trials (IMvigor011, TOMBOLA, MODERN) may establish its clinical utility as a standard tool for personalized disease management.

Ferroptosis is an oxidative, lipid peroxidation-driven form of regulated cell death that occurs when antioxidant and organelle-protective systems are compromised. Increasing evidence implicates ferroptosis as a process that can exert both tumour-suppressive and tumour-promoting effects depending on cellular context at multiple stages of cancer evolution (from tumour initiation to metastatic colonization), sparking substantial interest in therapeutically exploiting this mechanism of cell death. Yet, despite rapid preclinical progress, clinical translation of ferroptosis-based strategies remains nascent. In this Review, we examine the major barriers to translation, including pharmacological limitations, tumour-intrinsic heterogeneity, microenvironmental and immune constraints, and gaps in current preclinical modelling. We also highlight emerging opportunities such as new ferroptosis-inducing agents, biomarker-guided patient selection and rational combinations with chemotherapy, radiotherapy, targeted agents or immunotherapies. Finally, we outline a translational roadmap for integrating ferroptosis-based therapies into oncology practice. By defining key challenges and future directions, this Review aims to position ferroptosis as a viable therapeutic paradigm and to accelerate progress towards clinical application.

The gut microbiome is recognized as a determinant of response to immune checkpoint inhibitor (ICI) therapies in cancer. However, the clinical translation of microbiome science has been hampered by inconsistent definitions of dysbiosis, inadequate biomarker frameworks, and limited mechanistic understanding. In this review, we synthesize the current state of knowledge on how gut microbial composition and function influence ICI efficacy, highlighting both correlative and causal evidence. We discuss computational approaches based on α-diversity or taxonomic abundance and argue for more functionally and clinically informative models, such as the topological score (TOPOSCORE) and other dysbiosis indices derived from machine learning. Using retrospective analyses of metagenomic datasets from thousands of patients and healthy controls, we examine microbial patterns that distinguish responders from non-responders. We also explore how dysbiosis perturbs immunoregulatory pathways, including bile acid metabolism, gut permeability, and mucosal immunomodulation. Finally, we assess emerging therapeutic strategies aimed at correcting microbiome dysfunction — including dietary modification, bacterial consortia, and fecal microbiota transplantation — and describe how they are being deployed in multiple clinical trials. We conclude with a brief discussion of the ONCOBIOME initiative, which works with international partners to incorporate microbiome science into oncology workflows. By refining our understanding of gut–immune interactions and translating it into action, microbiome-informed oncology may unlock new therapeutic potential for patients previously resistant to immunotherapy.

Renal cell carcinoma (RCC) arises sporadically or in a hereditary context, with inherited cases accounting for less than 10%, depending on the genes analyzed. Next-generation sequencing has enabled the use of multigene panels (MGP) to characterize RCC linked to hereditary syndromes. The current French guidelines of the national reference network for hereditary renal cancers (PREDIR) recommend genetic testing for patients meeting specific clinical criteria. This study evaluates the diagnostic yield and the relevance of current criteria, the utility of MGP testing, and the added value of tumor analyses. We retrospectively analyzed 2057 RCC patients who underwent germline MGP testing across three French hospital laboratories. Tumor analysis results from 140 patients were also evaluated. The overall rate of germline pathogenic/likely pathogenic variants was 3.5%, with 39% in syndromic cases and 1.2% in apparently sporadic cases. Tumor analyses identified somatic pathogenic variants in 56.3% of cases. Our data support that the likelihood of identifying a germline PV is low in patients with sporadic single clear cell RCC, and that the clinical utility of testing all patients with other sporadic subtypes appears limited. This suggests a need to revise current testing criteria in patients with sporadic single RCC, for example, by lowering the age threshold for genetic testing from 45 to 40 years in clear cell RCC, and to 50 years in other subtypes. We also suggest incorporating tumor analyses to distinguish hereditary RCC from sporadic cases driven by tumor-specific pathogenic variants.