Daniela Conticelli
A5019891219- Genetic factors in colorectal cancer
- BRCA gene mutations in cancer
- Gastric Cancer Management and Outcomes
- Lung Cancer Treatments and Mutations
- Radiomics and Machine Learning in Medical Imaging
- Cancer Genomics and Diagnostics
- PARP inhibition in cancer therapy
- Helicobacter pylori-related gastroenterology studies
- Colorectal Cancer Treatments and Studies
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Ovarian cancer diagnosis and treatment
- Renal and related cancers
- Cancer Research and Treatments
- Animal Genetics and Reproduction
- Digestive system and related health
- Molecular Biology Techniques and Applications
- Cancer Cells and Metastasis
- DNA Repair Mechanisms
- Cytokine Signaling Pathways and Interactions
- Cancer-related gene regulation
- MicroRNA in disease regulation
- HER2/EGFR in Cancer Research
- Endoplasmic Reticulum Stress and Disease
- Cancer Mechanisms and Therapy
Candiolo Cancer Institute
2019-2024
University of Turin
2021-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2023
Microsatellite-unstable (MSI) cancers require WRN helicase to resolve replication stress due expanded DNA (TA)n dinucleotide repeats. is a promising synthetic lethal target for MSI tumors, and inhibitors are in development. In this study, we used CRISPR-Cas9 base editing map residues critical cells, validating the domain as primary drug target. Fragment-based screening led development of potent highly selective covalent inhibitors. These compounds selectively suppressed model growth vitro...
Abstract Drug resistance is a principal limitation to the long-term efficacy of cancer therapies. Cancer genome sequencing can retrospectively delineate genetic basis drug resistance, but this requires large numbers post-treatment samples nominate causal variants. Here we prospectively identify mechanisms ten oncology drugs from CRISPR base editing mutagenesis screens in four cell lines using guide RNA library predicted install 32,476 variants 11 genes. We functional classes protein...
Abstract Gastric cancer is the world's third leading cause of mortality. In spite significant therapeutic improvements, clinical outcome for patients with advanced gastric poor; thus, identification and validation novel targets extremely important from a point view. We generated wide, multilevel platform models, comprising 100 patient-derived xenografts (PDX), primary cell lines, organoids. Samples were classified according to their histology, microsatellite stability, Epstein–Barr virus...
Abstract Despite negative results of clinical trials conducted on the overall population patients with gastric cancer, PARP inhibitor (PARPi) therapeutic strategy still might represent a window opportunity for subpopulation cancer. An estimated 7% to 12% cancers exhibit mutational signature associated homologous recombination (HR) failure, suggesting that these could potentially benefit from PARPis. To analyze responsiveness cancer PARPi, we exploited gastroesophageal adenocarcinoma (GEA)...
Gastric and gastroesophageal adenocarcinomas represent the third leading cause of cancer mortality worldwide. Despite significant therapeutic improvement, outcome patients with advanced adenocarcinoma is poor. Randomized clinical trials failed to show a survival benefit in molecularly unselected treated anti-EGFR agents.
Abstract The DNA mismatch repair (MMR) system is a highly conserved pathway crucial for maintaining the genomic integrity. MMR impairment in sporadic tumors due to MLH1 epigenetic silencing or mutations other genes (such as MSH2, MSH6, PMS2) and leads microsatellite instability (MSI). Two independent molecular classifications reported existence of MSI subgroup gastric cancer (GC), including 22-23% all cases. GC inter intra-tumoral heterogeneity represents significant challenge precise...
Abstract Cytotoxic drugs often fail to eradicate cancers due the presence of treatment-persistent tumor cells that represent a reservoir for relapse. These “residual” cancer escape from chemotherapy- induced death by entering reversible slow proliferation state, known as drug tolerant persister (DTP) state. Although improvement treatment options achieved survival benefit, Gastric Cancer (GC) is still endowed with poor prognosis. Surgery and neo/adjuvant chemotherapy remain keystone...
<p>Supplementary Figure 1. Generating base editor-expressing MSI cell lines for screening. Supplementary 2. Quality control base-editor screens in lines. 3. Discovery and characterization of novel inhibitors WRN helicase. 4. Correlation inhibitor sensitivity with genetic molecular markers models. 5. Comparative analysis DNA damage MSS cells treated inactivation. 6: Effects GSK_WRN4 on colorectal cancer xenografts.</p>
<p>This table lists the results from Base editing screen</p>
<p>This file contains details of the BE sgRNA library</p>
<p>This file contain information on the Cell lines and organoids used in this study</p>
<div>Abstract<p>Microsatellite-unstable (MSI) cancers require WRN helicase to resolve replication stress due expanded DNA (TA)<sub>n</sub> dinucleotide repeats. is a promising synthetic lethal target for MSI tumors, and inhibitors are in development. In this study, we used CRISPR–Cas9 base editing map residues critical cells, validating the domain as primary drug target. Fragment-based screening led development of potent highly selective covalent inhibitors. These...
<p>Supplementary Figure 1. Generating base editor-expressing MSI cell lines for screening. Supplementary 2. Quality control base-editor screens in lines. 3. Discovery and characterization of novel inhibitors WRN helicase. 4. Correlation inhibitor sensitivity with genetic molecular markers models. 5. Comparative analysis DNA damage MSS cells treated inactivation. 6: Effects GSK_WRN4 on colorectal cancer xenografts.</p>
<p>This file contain information on the Cell lines and organoids used in this study</p>
<p>This table lists the results from Base editing screen</p>
<p>This file contains details of the BE sgRNA library</p>
<div>Abstract<p>Microsatellite-unstable (MSI) cancers require WRN helicase to resolve replication stress due expanded DNA (TA)<sub>n</sub> dinucleotide repeats. is a promising synthetic lethal target for MSI tumors, and inhibitors are in development. In this study, we used CRISPR–Cas9 base editing map residues critical cells, validating the domain as primary drug target. Fragment-based screening led development of potent highly selective covalent inhibitors. These...
<p>Microsatellite instability (MSI) phenotype in primary gastric tumours and their corresponding PDX/ organoid</p>
<div>Abstract<p>Gastric cancer is the world's third leading cause of mortality. In spite significant therapeutic improvements, clinical outcome for patients with advanced gastric poor; thus, identification and validation novel targets extremely important from a point view. We generated wide, multilevel platform models, comprising 100 patient-derived xenografts (PDX), primary cell lines, organoids. Samples were classified according to their histology, microsatellite stability,...
<div>Abstract<p>Gastric cancer is the world's third leading cause of mortality. In spite significant therapeutic improvements, clinical outcome for patients with advanced gastric poor; thus, identification and validation novel targets extremely important from a point view. We generated wide, multilevel platform models, comprising 100 patient-derived xenografts (PDX), primary cell lines, organoids. Samples were classified according to their histology, microsatellite stability,...
<p>Microsatellite instability (MSI) phenotype in primary gastric tumours and their corresponding PDX/ organoid</p>
<p>Organoids contain few or no stroma component and when reinjected in mice originated tumors resembling the corresponding PDXs.</p>