Champalimaud Foundation

AmpliconSuite: an end-to-end workflow for analyzing focal amplifications in cancer genomes

Abstract Here we present AmpliconSuite, a toolkit for focal amplification analysis from cancer whole-genome sequencing that identifies extrachromosomal DNA (ecDNA), breakage–fusion–bridges and other amplification modes. Its ecContext module categorizes ecDNA structures to underst...

Distinct migratory dendritic cell subsets cooperate to prime tissue-resident memory-like CD8⁺ T cells in mouse tumors

Tumor-infiltrating tissue-resident memory (TRM)-like CD8+ T cells correlate with positive prognosis and better responses to cancer immunotherapy, yet the mechanisms underlying their specification remain ill-understood. Here, we use the KP (KrasG12D, p53-/-) mouse model of lung ad...

Randomised phase III trials of cancer prevention drugs: a systematic review and prediction of trial success

BACKGROUND: Pharmacological cancer risk reduction has received far less investment than therapeutic oncology and only a few agents have entered routine practice. Understanding the predictors of positive outcomes of previous trials and issues faced is critical to future developmen...

Prognostic Role of Adverse Events in a Worldwide Population of Patients with Biliary Tract Cancer Treated with Chemo-Immunotherapy

Background: Biliary tract cancers (BTCs) are aggressive malignancies with limited treatment options. The addition of durvalumab or pembrolizumab to cisplatin–gemcitabine improves overall survival (OS), but validated biomarkers of benefit remain limited. Immune-mediated adverse ev...

POU4F3 variants are prevalent in Chinese patients with autosomal dominant non-syndromic hearing loss and concurrent tinnitus

POU4F3 (DFNA15) is an established causative gene for autosomal dominant non-syndromic hearing loss (ADNSHL); however, its mutational spectrum in the Chinese population remains incompletely characterized. This study aimed to expand the mutational spectrum of POU4F3 in the Chinese...

Bifunctional Phagocytic Synapse Enhancers Remodel the Tumor Microenvironment to Overcome Immunosuppression

Abstract Current immunotherapies often fail in immunologically “cold”, macrophage-rich tumor microenvironments (TMEs). Multi-targeting approaches that modulate innate-adaptive immune activation represent a promising frontier in cancer immunotherapy. Here, we developed phagocytic...

Myeloma Elderly Prognostic Score ( MEPS ): A Proposed Prognostic Score Integrating Age, Renal Function, Performance Status, and Ultra‐High‐Risk Cytogenetics

Established disease-centered prognostic systems may be less tailored to elderly/non-transplant-eligible (NTE) patients with multiple myeloma (MM), in whom host-related factors such as age, performance status, and renal function strongly influence all-cause outcomes. We developed...

Navigating Uncharted Waters: Steering the Course and Confronting Challenges of Brain Metastases in EGFR-Mutant Non-Small Cell Lung Cancer

Brain metastases represent a major clinical challenge in the management of non-small-cell lung cancer, particularly in patients with epidermal growth factor receptor mutations, constituting a leading cause of morbidity and mortality. In recent years, significant advancements have...

Neural substrates of female sexual rejection: hypothalamic pathways to the periaqueductal gray

Abstract Selecting an appropriate behavioral response according to one’s internal state is essential for well-being. Across the reproductive cycle, fluctuating levels of sex hormones align female behavior with reproductive capacity by modulating neuronal circuits that express hor...