A5021411537- Colorectal Cancer Treatments and Studies
- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Cancer Treatment and Pharmacology
- Cancer Research and Treatments
- Cancer Cells and Metastasis
- HER2/EGFR in Cancer Research
- Protein Degradation and Inhibitors
- Nanoparticle-Based Drug Delivery
- Radiomics and Machine Learning in Medical Imaging
- Glycosylation and Glycoproteins Research
- Gastric Cancer Management and Outcomes
- Genetic factors in colorectal cancer
- Pancreatic and Hepatic Oncology Research
- Health Systems, Economic Evaluations, Quality of Life
- Advanced Proteomics Techniques and Applications
- Ubiquitin and proteasome pathways
- Ferroptosis and cancer prognosis
- Cancer Immunotherapy and Biomarkers
- Cell death mechanisms and regulation
- Prostate Cancer Treatment and Research
- CAR-T cell therapy research
- Cancer-related Molecular Pathways
- Cancer-related gene regulation
- Immunotherapy and Immune Responses
Candiolo Cancer Institute
2016-2024
University of Turin
2016-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2018-2021
Mayo Clinic
2018
WinnMed
2018
Heidelberg University
2018
Fondazione Piemontese per la Ricerca sul Cancro Onlus
2016
Method12 April 2019Open Access Transparent process INKA, an integrative data analysis pipeline for phosphoproteomic inference of active kinases Robin Beekhof orcid.org/0000-0002-9500-528X Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit The Netherlands OncoProteomics Laboratory, Search more papers by this author Carolien van Alphen Alex A Henneman orcid.org/0000-0002-3746-4410 Jaco C Knol Thang V Pham Frank Rolfs Mariette Labots Evan Henneberry Tessa YS Le Large...
Blockade of epidermal growth factor receptor (EGFR) causes tumor regression in some patients with metastatic colorectal cancer (mCRC). However, residual disease reservoirs typically remain even after maximal response to therapy, leading relapse. Using patient-derived xenografts (PDXs), we observed that mCRC cells surviving EGFR inhibition exhibited gene expression patterns similar those a quiescent subpopulation normal intestinal secretory precursors Paneth cell characteristics. Compared...
Epidermal growth factor receptor (EGFR) is a well-exploited therapeutic target in metastatic colorectal cancer (mCRC). Unfortunately, not all patients benefit from current EGFR inhibitors. Mass spectrometry-based proteomics and phosphoproteomics were performed on 30 genomically pharmacologically characterized mCRC patient-derived xenografts (PDXs) to investigate the molecular basis of response blockade identify alternative drug targets overcome resistance. Both tyrosine global...
HER2 amplification occurs in approximately 5% of colorectal cancer (CRC) cases and is associated only partially with clinical response to combined human epidermal growth factor receptor 2 (HER2)/epidermal (EGFR)-targeted treatment. An alternative approach based on adoptive cell therapy using T cells engineered anti-HER2 chimeric antigen (CAR) proved be toxic due on-target/off-tumor activity. Here we describe a combinatorial strategy safely target carcinoembryonic (CEA) expression CRC...
The breadth and depth at which cancer models are interrogated contribute to the successful clinical translation of drug discovery efforts. In colorectal (CRC), model availability is limited by a dearth large-scale collections patient-derived xenografts (PDXs) paired tumoroids from metastatic disease, where experimental therapies typically tested. Here we introduce XENTURION, an open-science resource offering platform 128 PDX patients with CRC, along matched PDX-derived tumoroids....
// Michela Boi 1, 2, * , Maria Todaro Valentina Vurchio 1 Shao Ning Yang 3 John Moon Ivo Kwee 4, 5, 6 Andrea Rinaldi 4 Heng Pan 7, 8 Ramona Crescenzo 2 Mangeng Cheng 9 Leandro Cerchietti Olivier Elemento E. Riveiro 10 Esteban Cvitkovic 10, 11 Francesco Bertoni 12 Giorgio Inghirami 13 The AIRC 5xMille Consortium 'Genetics-Driven Targeted Management of Lymphoid Malignancies' Department Molecular Biotechnology and Health Science Center for Experimental Research Medical Studies (CeRMS),...
Abstract DNA sequence mutability in tumors with chromosomal instability is conventionally believed to remain uniform, constant, and low, based on the assumption that further mutational accrual a context of marked aneuploidy evolutionarily disadvantageous. However, this concept lacks robust experimental verification. We adapted principles mutation accumulation experiments, traditionally performed lower organisms, clonal populations patient-derived tumoroids empirically measured spontaneous...
Colorectal cancer (CRC) is a heterogeneous disease showing significant variability in clinical aggressiveness. Primary and acquired resistance limits the efficacy of available treatments, identification effective drug combinations needed to further improve patients’ outcomes. We previously found that NEDD8-activating enzyme inhibitor pevonedistat induced tumor stabilization preclinical models poorly differentiated, clinically aggressive CRC resistant therapies. To identify drugs can be...
Abstract Purpose: Approximately 20% of patients with RAS wild-type metastatic colorectal cancer (mCRC) experience objective responses to the anti-EGFR antibody cetuximab, but disease eradication is seldom achieved. The extent tumor shrinkage correlates long-term outcome. We aimed find rational combinations that potentiate cetuximab efficacy by disrupting adaptive dependencies on antiapoptotic molecules (BCL2, BCL-XL, MCL1). Experimental Design: Experiments were conducted in patient-derived...
ABSTRACT The breadth and depth at which cancer models are interrogated contribute to successful translation of drug discovery efforts the clinic. In colorectal (CRC), model availability is limited by a dearth large-scale collections patient-derived xenografts (PDXs) paired tumoroids from metastatic disease, setting where experimental therapies typically tested. XENTURION unique open-science resource that combines platform 129 PDX sister matched PDX-derived (PDXTs) patients with CRC,...
Abstract Introduction. The activity of BET inhibitors in several models human hematologic disorders, including multiple myeloma (MM) has recently been demonstrated. Exposure cancer cells to results a significant down-regulation c-Myc expression, and suppression transcriptional programs associated with proliferation survival. OTX015 is new selective orally bioavailable inhibitor the family proteins clinical development. We evaluated its panel MM known upregulation c-MYC pathway. Materials...
Abstract Rationale: The HERACLES A trial showed that a clinical sizeable subset of 3% metastatic colorectal cancers (mCRC), identifiable by the amplification HER2 gene, can be targeted for effective, durable and safe anti-HER2 treatment with combination small molecule kinase inhibitor lapatinib (L) monoclonal antibody trastuzumab (T) [Siena et al. J Clin Oncol 33, 2015.(suppl; abs 3508)]. As any other therapy, however, L+T was not active in all patients, even responders its efficacy limited...
Abstract Introduction: Inhibitors of the bromodomain and extraterminal (BET) family (BRD2, BRD3, BRD4, BRDT) are a promising new class anticancer agents. Here, we assessed activity mechanism action novel molecule OTX015, selective orally bioavailable BRD2/3/4 inhibitor, in panel anaplastic large cell lymphoma (ALCL) lines. Material Methods: Human lines derived from ALKpos ALCL (SUPM2/TS, SU-DHL-1, L82, JB-6, Karpas 299) were treated with increasing doses OTX015 (OncoEthix SA, Swtizerland)....
Abstract Strong evidence supports the use of patient-derived xenografts (PDXs) as faithful models reflecting patient outcomes. Since not all research can support animals, exploiting in vitro such organoids (also know tumoroids) is essential. However, current biobanks metastatic colorectal cancer (mCRC) tumoroids have important limitations, small sample size and a lack systematic vivo validation with paired xenografts, which decreases translational value tumoroid-based pipelines. Here we...
Abstract HER2 amplification occurs in about 5% of colorectal cancers (CRC) and is only partially associated with clinical response to combined HER2/EGFR targeted treatment. An alternative approach, based on Adoptive Cell Therapy (ACT) using T cells engineered anti-HER2 Chimeric Antigen Receptor (CAR), proved toxic due "on-target off-tumor" activity. Therefore, we developed a combinatorial ACT strategy safely target CRC synNotch-based artificial regulatory network. A synthetic Notch receptor...
<div>AbstractPurpose:<p>Approximately 20% of patients with RAS wild-type metastatic colorectal cancer (mCRC) experience objective responses to the anti-EGFR antibody cetuximab, but disease eradication is seldom achieved. The extent tumor shrinkage correlates long-term outcome. We aimed find rational combinations that potentiate cetuximab efficacy by disrupting adaptive dependencies on antiapoptotic molecules (BCL2, BCL-XL, MCL1).</p>Experimental Design:<p>Experiments...
<p>Correlations between transcript expression of pro/anti-apoptotic proteins and response to combination therapy withcetuximab BH3 mimetics.</p>
<p>EGFR inhibition does not affect BIM protein levels in cetuximab-resistant PDXs.</p>
<p>Effect of BCL-XL inhibition on tumor growth in mCRC PDXs.</p>
<p>Statistical analysis of results shown in Figure 2.</p>
<p>EGFR inhibition does not induce BIM upregulation in cetuximab-resistant PDXOs.</p>
<p>EGFR inhibition does not induce BIM upregulation in cetuximab-resistant PDXOs.</p>