Frank van Gemert
A5102915373- Advanced Breast Cancer Therapies
- Cancer Treatment and Pharmacology
- Cancer, Hypoxia, and Metabolism
- Cell Image Analysis Techniques
- Cancer Research and Treatments
- bioluminescence and chemiluminescence research
- DNA Repair Mechanisms
- Cancer, Stress, Anesthesia, and Immune Response
- Computational Drug Discovery Methods
- Endoplasmic Reticulum Stress and Disease
- Biological Research and Disease Studies
- Cancer-related Molecular Pathways
- CAR-T cell therapy research
- Melanoma and MAPK Pathways
- PARP inhibition in cancer therapy
- Protein Degradation and Inhibitors
- Microtubule and mitosis dynamics
- Enzyme function and inhibition
- Histone Deacetylase Inhibitors Research
- 3D Printing in Biomedical Research
- RNA regulation and disease
- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Ubiquitin and proteasome pathways
The Netherlands Cancer Institute
2021-2024
Oncode Institute
2024
Abstract Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress response programs that counteract the inherent toxicity such aberrant signaling. Although inhibition signaling has been explored extensively, there is increasing evidence overactivation same can also disrupt cancer cause lethality. We show here protein phosphatase 2A (PP2A) hyperactivates multiple engages responses in colon cells. Genetic compound screens...
Abstract Background Liver cancer is one of the most commonly diagnosed cancers and fourth leading cause cancer-related death worldwide. Broad-spectrum kinase inhibitors like sorafenib lenvatinib provide only modest survival benefit to patients with hepatocellular carcinoma (HCC). This study aims identify novel therapeutic strategies for HCC patients. Methods Integrated bioinformatics analyses a non-biased CRISPR loss function genetic screen were performed potential targets cells....
<div>Abstract<p>Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress response programs that counteract the inherent toxicity such aberrant signaling. Although inhibition signaling has been explored extensively, there is increasing evidence overactivation same can also disrupt cancer cause lethality. We show here protein phosphatase 2A (PP2A) hyperactivates multiple engages responses in colon cells. Genetic...
ABSTRACT Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress-response programs that counteract the inherent toxicity such aberrant signaling. While inhibition signaling has been explored extensively, there is increasing evidence overactivation same can also disrupt cancer cause lethality. We show here Protein Phosphatase 2A (PP2A) hyperactivates multiple engages stress responses in colon cells. Genetic compound screens...
Abstract Impaired control of the G1/S checkpoint allows initiation DNA replication under non-permissive conditions. Unscheduled S-phase entry is associated with stress, demanding for other checkpoints or cellular pathways to maintain proliferation. Here, we uncovered a requirement ADARp150 sustain proliferation G1/S-checkpoint-defective cells growth-restricting Besides its well-established mRNA editing function in inversely oriented short interspersed nuclear elements (SINEs), found exert...
<p>Figure S9: Single-cell RNAseq identify transcriptional signatures downregulated in CRC cells after acquired resistance to the combination of LB-100 and adavosertib UMAP representations HT-29 (A) SW-480 (B) colored by activity scores for indicated pathways. UMAPs sample origin from both cell lines are present left reference. The boxen plots show pathway parental (red) resistant (blue) cells.</p>
<p>Supplementary table 6: Stress-focused drug screens AUC differences in SW-480 cells Area Under the Curve (AUC) from each compound of stress-focused screen presence or absence LB-100. Compounds are ranked by difference between LB-100-treated and untreated samples.</p>
<p>Supplementary table 3: Full list of genes whose knockout attenuated LB-100 toxicity in SW-480 cells the CRISPR-KO screen FDR smaller or equal to 0.25 and log2 fold change greater 1 treated/untreated comparison were criteria for hit selection.</p>
<p>Supplementary table 1: Cancer cell lines with oncogenic drivers The mutational status of the was compiled from ATCC, Catalogue Somatic Mutations in (COSMIC) and Cell Model Passport, Wellcome Trust Sanger Institute, Depmap portal databases.</p>
<p>Supplementary table 4: The composition of the stress-focused drug library Compounds comprising with their respective targets.</p>
<p>Supplementary table 4: The composition of the stress-focused drug library Compounds comprising with their respective targets.</p>
<p>Figure S7: Normal tissues from the orthotopic CRC PDXs are not affected by LB-100, adavosertib, or combination. Representative Hematoxylin & Eosin (H&E) stainings of heart, liver, lung, and spleen PDOX1 treated as indicated. Original magnifications indicated.</p>
<p>Supplementary table 5: Stress-focused drug screens AUC differences in HT-29 cells Area Under the Curve (AUC) from each compound of stress-focused screen presence or absence LB-100. Compounds are ranked by difference between LB-100-treated and untreated samples.</p>
<p>Figure S9: Single-cell RNAseq identify transcriptional signatures downregulated in CRC cells after acquired resistance to the combination of LB-100 and adavosertib UMAP representations HT-29 (A) SW-480 (B) colored by activity scores for indicated pathways. UMAPs sample origin from both cell lines are present left reference. The boxen plots show pathway parental (red) resistant (blue) cells.</p>
<p>Figure S8: Acquired resistance to the combination of LB-100 and adavosertib suppressed malignant traits in CRC models (A) IncuCyte-based proliferation assays from HT-29 SW-480 parental resistant cells absence or presence (LB-100 4 µM + 400 nM). (B) Chromosome counting representative chromosome spreads cells. Nocodazole was added for 3h block mitosis. Cells were harvested by mitotic shake-off spreading. Over 40 (HT-29 HT-29-R) 50 (SW-480 SW-480-R) counted per cell line. Asterisks...
<p>Figure S7: Normal tissues from the orthotopic CRC PDXs are not affected by LB-100, adavosertib, or combination. Representative Hematoxylin & Eosin (H&E) stainings of heart, liver, lung, and spleen PDOX1 treated as indicated. Original magnifications indicated.</p>
<p>Supplementary table 7: Full list of genes whose knockout was selectively toxic in the presence LB-100 SW-480 cells CRISPR-KO screen FDR smaller or equal to 0.25 and log2 fold change -1 treated/untreated comparison were criteria for hit selection.</p>
<p>Supplementary table 2: Full list of genes whose overexpression was selectively toxic in the presence LB-100 HT-29 cells CRISPRa screen FDR smaller or equal to 0.25 and log2 fold change -1 treated/untreated comparison were criteria for hit selection.</p>
<p>Supplementary table 1: Cancer cell lines with oncogenic drivers The mutational status of the was compiled from ATCC, Catalogue Somatic Mutations in (COSMIC) and Cell Model Passport, Wellcome Trust Sanger Institute, Depmap portal databases.</p>
<p>Supplementary table 2: Full list of genes whose overexpression was selectively toxic in the presence LB-100 HT-29 cells CRISPRa screen FDR smaller or equal to 0.25 and log2 fold change -1 treated/untreated comparison were criteria for hit selection.</p>
<p>Supplementary table 6: Stress-focused drug screens AUC differences in SW-480 cells Area Under the Curve (AUC) from each compound of stress-focused screen presence or absence LB-100. Compounds are ranked by difference between LB-100-treated and untreated samples.</p>
<p>Supplementary table 5: Stress-focused drug screens AUC differences in HT-29 cells Area Under the Curve (AUC) from each compound of stress-focused screen presence or absence LB-100. Compounds are ranked by difference between LB-100-treated and untreated samples.</p>
<p>Supplementary table 7: Full list of genes whose knockout was selectively toxic in the presence LB-100 SW-480 cells CRISPR-KO screen FDR smaller or equal to 0.25 and log2 fold change -1 treated/untreated comparison were criteria for hit selection.</p>
<p>Supplementary table 3: Full list of genes whose knockout attenuated LB-100 toxicity in SW-480 cells the CRISPR-KO screen FDR smaller or equal to 0.25 and log2 fold change greater 1 treated/untreated comparison were criteria for hit selection.</p>
<div>Abstract<p>Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress response programs that counteract the inherent toxicity such aberrant signaling. Although inhibition signaling has been explored extensively, there is increasing evidence overactivation same can also disrupt cancer cause lethality. We show here protein phosphatase 2A (PP2A) hyperactivates multiple engages responses in colon cells. Genetic...