0000000000150133
AUTHOR
Hans M. Rodermond
showing 6 related works from this author
A multidimensional network approach reveals microRNAs as determinants of the mesenchymal colorectal cancer subtype
2016
Colorectal cancer (CRC) is a heterogeneous disease posing a challenge for accurate classification and treatment of this malignancy. There is no common genetic molecular feature that would allow for the identification of patients at risk for developing recurrences and thus selecting patients who would benefit from more stringent therapies still poses a major clinical challenge. Recently, an international multicenter consortium (CRC Subtyping Consortium) was established aiming at the classification of CRC patients in biologically homogeneous CRC subtypes. Four consensus molecular subtypes (CMSs) were identified, of which the mesenchymal CMS4 presented with worse prognosis signifying the impor…
Wnt activity defines colon cancer stem cells and is regulated by the microenvironment.
2010
Despite the presence of mutations in APC or beta-catenin, which are believed to activate the Wnt signalling cascade constitutively, most colorectal cancers show cellular heterogeneity when beta-catenin localization is analysed, indicating a more complex regulation of Wnt signalling. We explored this heterogeneity with a Wnt reporter construct and observed that high Wnt activity functionally designates the colon cancer stem cell (CSC) population. In adenocarcinomas, high activity of the Wnt pathway is observed preferentially in tumour cells located close to stromal myofibroblasts, indicating that Wnt activity and cancer stemness may be regulated by extrinsic cues. In agreement with this noti…
Consensus molecular subtypes of colorectal cancer are recapitulated in in vitro and in vivo models
2018
Colorectal cancer (CRC) is a highly heterogeneous disease both from a molecular and clinical perspective. Several distinct molecular entities, such as microsatellite instability (MSI), have been defined that make up biologically distinct subgroups with their own clinical course. Recent data indicated that CRC can be best segregated into four groups called consensus molecular subtypes (CMS1-4), each of which has a unique biology and gene expression pattern. In order to develop improved, subtype-specific therapies and to gain insight into the molecular wiring and origin of these subtypes, reliable models are needed. This study was designed to determine the heterogeneity and identify the prese…
Abstract 3193: Development of a colon cancer model system reveals epithelial contribution to poor-prognosis gene signatures
2016
Abstract Background: Recent consensus on molecular classification categorizes colorectal cancer (CRC) into 4 robust subtypes: CMS1 (epithelial-MSI), CMS2 (epithelial-canonical), CMS3 (epithelial-metabolic) and CMS4 (mesenchymal)1. CMS4 is linked to poor cancer prognosis and characterized by mesenchymal and epithelial-to-mesenchymal transition (EMT) gene expression2,3. Recent attempts to deconvolute the transcriptome from CRC tumors have suggested that the mesenchymal gene expression results from a large stromal compartment and is not due to epithelial cells with EMT-like features4,5. This challenges the classic notion that tumor cells activate the EMT program to undergo trans-differentiatio…
Targeting DNA double strand break repair with hyperthermia and DNA-PKcs inhibition to enhance the effect of radiation treatment
2016
// Bregje van Oorschot 1 , Giovanna Granata 1 , Simone Di Franco 2 , Rosemarie ten Cate 1 , Hans M. Rodermond 1 , Matilde Todaro 3 , Jan Paul Medema 1 , Nicolaas A.P. Franken 1 1 Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Experimental Molecular Medicine, Department of Radiation Oncology, Academic Medical Center, Cancer Genomics Center, Amsterdam, The Netherlands 2 Department of Surgical, Oncological and Stomatological Sciences (DICHIRONS), Cellular and Molecular Pathophysiology Laboratory, University of Palermo, Palermo, Italy 3 Biomedical Department of Internal and Specialistic Medicine (DIBIMIS), University of Palermo, Palermo, Italy Correspondence to: Nicol…
Capturing colorectal cancer inter-tumor heterogeneity in patient-derived xenograft (PDX) models
2018
Patient-derived xenograft (PDX) models have become an important asset in translational cancer research. However, to provide a robust preclinical platform, PDXs need to accommodate the tumor heterogeneity that is observed in patients. Colorectal cancer (CRC) can be stratified into four consensus molecular subtypes (CMS) with distinct biological and clinical features. Surprisingly, using a set of CRC patients, we revealed the partial representation of tumor heterogeneity in PDX models. The epithelial subtypes, the largest subgroups of CRC subtype, were very ineffective in establishing PDXs, indicating the need for further optimization to develop an effective personalized therapeutic approach …