A5051358028- Colorectal Cancer Treatments and Studies
- Genetic factors in colorectal cancer
- Cancer Genomics and Diagnostics
- Pancreatic and Hepatic Oncology Research
- Cancer Cells and Metastasis
- Intraperitoneal and Appendiceal Malignancies
- Hepatocellular Carcinoma Treatment and Prognosis
- Pancreatic function and diabetes
- Digestive system and related health
- Cancer Treatment and Pharmacology
- Pancreatitis Pathology and Treatment
- Endoplasmic Reticulum Stress and Disease
- Genomic variations and chromosomal abnormalities
- Enzyme Structure and Function
- Colorectal Cancer Screening and Detection
- Cancer-related molecular mechanisms research
- Renal cell carcinoma treatment
- Molecular Biology Techniques and Applications
- Nanoparticle-Based Drug Delivery
- Heat shock proteins research
- Microfluidic and Capillary Electrophoresis Applications
- Wnt/β-catenin signaling in development and cancer
- 3D Printing in Biomedical Research
- Single-cell and spatial transcriptomics
- Innovative Microfluidic and Catalytic Techniques Innovation
University of Amsterdam
2018-2025
Amsterdam University Medical Centers
2018-2025
Oncode Institute
2021-2025
Cancer Center Amsterdam
2022-2025
Dutch Cancer Society
2022
Amsterdam UMC Location University of Amsterdam
2018
A significant proportion of colorectal cancer (CRC) patients develop peritoneal metastases (PM) in the course their disease. PMs are associated with a poor quality life, morbidity and dismal disease outcome. To improve care for this patient group, better understanding molecular characteristics CRC-PM is required. Here we present comprehensive characterization cohort 52 patients. This reveals that represent distinct CRC subtype, CMS4, but can be further divided three separate categories, each...
Survival rates of cancer patients vary widely within and between malignancies. While genetic aberrations are at the root all cancers, individual genomic features cannot explain these distinct disease outcomes. In contrast, intra-tumour heterogeneity (ITH) has potential to elucidate pan-cancer survival biology that drives prognosis. Unfortunately, a comprehensive effective framework measure ITH across cancers is missing. Here, we introduce scalable chromosomal copy number (CNH) predicts...
Significance Colorectal cancer (CRC) is a heterogeneous disease, with significant variation in genotype and phenotype within each individual tumor. This intratumor heterogeneity emerges during tumor development due to clonal evolution part can explain therapy resistance CRC. However, detailed understanding of the spatiotemporal tumors underlying remains absent. Here, we use lineage-tracing experiments human CRC cells transplanted into immunocompromised mice, combination computational...
Consensus Molecular Subtype (CMS) classification of colorectal cancer (CRC) tissues is complicated by RNA degradation upon formalin-fixed paraffin-embedded (FFPE) preservation. Here, we present an FFPE-curated CMS classifier. The CMSFFPE classifier was developed using genes with a high transcript integrity in FFPE-derived RNA. We evaluated the accuracy two FFPE-RNA datasets matched fresh-frozen (FF) data, and FF-derived set. An application cohort metastatic CRC patients established, partly...
Clonal dispersal, resulting from the intermingling of tumor cell subpopulations, is thought to be a key driver heterogeneity. Despite advances in spatial modeling cancer biology, quantification clonal dispersal has been challenging. This study introduces straightforward method, relying on fluorescent barcoding, quantify various vitro and vivo models colorectal (CRC). Our approach allows for precise localization clones uncovering degree mixing across different CRC models. findings suggest...
The tissue dynamics that govern maintenance and regeneration of the pancreas remain largely unknown. In particular, presence nature a cellular hierarchy remains topic debate. Previous lineage tracing strategies in relied on specific marker genes for clonal labeling, which left other populations untested failed to account potential widespread phenotypical plasticity. Here we employed system depends replication-induced marks. We found that, homeostasis, steady acinar replacement events...
Colorectal cancer (CRC) can be divided into four consensus molecular subtypes (CMS), each with distinct biological features. CMS4 is associated epithelial-mesenchymal transition and stromal infiltration (Guinney et al., Nat Med 21:1350-6, 2015; Linnekamp Cell Death Differ 25:616-33, 2018), whereas clinically it characterized by lower responses to adjuvant therapy, higher incidence of metastatic spreading hence dismal prognosis (Buikhuisen Oncogenesis 9:66, 2020).To understand the biology...
Highlights•Marker-free lineage tracing and modeling reveal pancreatic cancer growth dynamics•Clonogenicity of cells is fully defined by the microenvironment•Stromal Hh inhibition impacts on clonal dynamics, but not tumor growthSummaryEffective treatments for ductal adenocarcinoma (PDAC) are lacking, targeted agents have demonstrated limited efficacy. It has been speculated that a rare population stem (CSCs) drives growth, therapy resistance, rapid metastatic progression in PDAC. These CSCs...
Peritoneal metastases (PMs) from colorectal cancer (CRC) respond poorly to treatment and are associated with unfavorable prognosis. For example, the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) cytoreductive surgery in resectable patients shows limited benefit, novel treatments urgently needed. The majority CRC-PMs represent CMS4 molecular subtype CRC, here we queried vulnerabilities this pharmacogenomic databases identify therapies. This reveals copper ionophore elesclomol...
Background Aberrant Wnt pathway activation is a key driver of colorectal cancer (CRC) and essential to sustain tumour growth progression. Although the downstream protein-coding target genes cascade are well known, long non-coding transcriptome has not yet been fully resolved. Objective In this study, we aim comprehensively reveal Wnt-regulated exploit molecules as novel therapeutic targets. Design We used global run-on sequencing define β-catenin-regulated RNAs (lncRNAs) in CRC. CRISPRi...
The cancer xenograft model in which human cells are implanted a mouse is one of the most used preclinical models to test efficacy novel drugs. However, imperfect; animal ethically burdened, and imperfect predictions contribute high clinical attrition If microfluidic cancer-on-chip could recapitulate key elements model, then these substitute subsequently surpass by reducing variation, increasing sensitivity scale, adding factors. Here, we exposed HCT116 colorectal spheroids dynamic,...
Background: Although a wealth of knowledge has been gathered on normal pancreatic tissue maintenance and repair following injury, some fundamental questions remain. These pertain for instance to the existence contributions stem-like cells, plasticity cell fates. Lineage tracing studies from predefined populations have performed but these are invariably plagued by priori assumptions origin. Methods: Using quantitative analyses marker-free stochastic lineage mouse model in healthy tissue, we...
The tissue dynamics that govern maintenance and regeneration of the pancreas remain largely unknown. In particular, presence nature a cellular hierarchy remains topic debate. Previous lineage tracing strategies in relied on specific marker genes for clonal labeling, which leaves other populations untested fails to account potential widespread phenotypical plasticity. Here we employed system depends replication-induced marks. We found homeostasis, steady acinar replacement events characterize...
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest human malignancies. Effective treatment options are currently lacking, and targeted agents have so far demonstrated limited efficacy. It has been speculated that a rare population cancer stem cells (CSCs) drives growth, therapy resistance, rapid metastatic progression in PDAC. These CSCs characterized by expression genes associated with immature cells, demonstrate high clonogenicity vitro tumorigenic potential vivo. However,...