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SPICE SIGNED

Synthetic Lethal Phenotype Identification through Cancer Evolution Analysis

Total Cost €

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EC-Contrib. €

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Partnership

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 SPICE project word cloud

Explore the words cloud of the SPICE project. It provides you a very rough idea of what is the project "SPICE" about.

disease    mutations    synthetic    completion    public    tumours    vitro    cancer    genetically    performed    exist    gain    potent    generation    biomarkers    cell    mutually    tumour    secondary    events    harbour    chart    computational    invasion    recurs    expertise    heterogeneous    samples    heel    mathematical    evolution    lethality    resistant    mining    stand    advantage    treatment    migration    exclusive    alterations    clues    positing    readouts    validations    despite    successful    driver    drivers    leverage    resistance    cancers    achilles    combinations    algorithms    dna    androgens    create    unravel    manner    datasets    summary    uncover    sequencing    cas9    genetic    experiments    hormonal    nominate    patient    prostate    landscape    shrna    nominating    tet    assays    transform    recalcitrant    methodology    lines    candidate    occurring    anti    genomics    private    crispr    validated    data    prior    cycle    1000    clinical    prioritize    genes    erc    drugs    pca    lethal    candidates    led    aggressive    crpc    therapy    innovative    epigenetic    genomic    model    trials    castration    lineage    approved    function   

Project "SPICE" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITA DEGLI STUDI DI TRENTO 

Organization address
address: VIA CALEPINA 14
city: TRENTO
postcode: 38122
website: www.unitn.it

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Italy [IT]
 Project website http://demichelislab.eu/projects/synthetic-lethal-phenotype-identification-through-cancer-evolution-analysis
 Total cost 1˙996˙428 €
 EC max contribution 1˙996˙428 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-10-01   to  2020-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITA DEGLI STUDI DI TRENTO IT (TRENTO) coordinator 1˙996˙428.00

Map

 Project objective

Prostate cancer (PCA) is a genetically heterogeneous disease. Advances in targeted hormonal therapy (second generation anti-androgens) have led to more effective management of castration-resistant prostate cancer (CRPC). Despite these highly potent drugs, disease recurs with new genomic and epigenetic alterations. In this ERC proposal, I will leverage my expertise in cancer genomics and a new computational methodology to unravel the landscape of lethal PCA, with a focus on determining the Achilles’ heel of these aggressive tumours. In Aim 1, I will take advantage of DNA sequencing data from over 1000 patient-derived tumour samples and use highly innovative mathematical algorithms to create a detailed evolution chart for each tumour and identify driver events leading to CRPC. After nominating candidate drivers, we propose testing 10 using in vitro gain- and loss-of-function validations experiments (i.e., CRISPR/Cas9, shRNA, and Tet-On assays) in PCA cell lines using migration, invasion, and cell cycle as readouts. In Aim 2, I will focus on genomic events that occur in recalcitrant CRPC, positing that genetic alterations occurring prior or secondary to treatment harbour clues into resistance. In vitro validations will be performed on the top 10 biomarkers. In Aim 3, I will nominate synthetic lethality combinations by mining CRPC genomic data taken from Stand Up 2 Cancer CRPC clinical trials. I will prioritize mutually exclusive genomic alterations in genes for which approved drugs exist. The top 5-10 candidates will be validated in a prostate lineage-specific manner. In summary, this ERC proposal will leverage my many years of expertise in PCA genomics and emerging public and private CRPC datasets to uncover driver mutations that will enhance our understanding of recalcitrant CRPC. Successful completion of this study should lead to novel treatment approaches for CRPC and to a computational model that may transform our approach to evaluating other cancers.

 Publications

year authors and title journal last update
List of publications.
2017 Alessandro Romanel, Tuo Zhang, Olivier Elemento, Francesca Demichelis
EthSEQ: ethnicity annotation from whole exome sequencing data
published pages: 2402-2404, ISSN: 1367-4803, DOI: 10.1093/bioinformatics/btx165
Bioinformatics 33/15 2019-06-06
2017 David J. Pisapia, Steven Salvatore, Chantal Pauli, Erika Hissong, Ken Eng, Davide Prandi, Verena-Wilbeth Sailer, Brian D. Robinson, Kyung Park, Joanna Cyrta, Scott T. Tagawa, Myriam Kossai, Jacqueline Fontugne, Robert Kim, Alexandros Sigaras, Rema Rao, Danielle Pancirer, Bishoy Faltas, Rohan Bareja, Ana M. Molina, David M. Nanus, Prajwal Rajappa, Mark M. Souweidane, Jeffrey Greenfield, Anne-Katrin Emde, Nicolas Robine, Olivier Elemento, Andrea Sboner, Francesca Demichelis, Himisha Beltran, Mark A. Rubin, Juan Miguel Mosquera
Next-Generation Rapid Autopsies Enable Tumor Evolution Tracking and Generation of Preclinical Models
published pages: 1-13, ISSN: 2473-4284, DOI: 10.1200/PO.16.00038
JCO Precision Oncology 1 2019-06-06
2016 Himisha Beltran, Davide Prandi, Juan Miguel Mosquera, Matteo Benelli, Loredana Puca, Joanna Cyrta, Clarisse Marotz, Eugenia Giannopoulou, Balabhadrapatruni V S K Chakravarthi, Sooryanarayana Varambally, Scott A Tomlins, David M Nanus, Scott T Tagawa, Eliezer M Van Allen, Olivier Elemento, Andrea Sboner, Levi A Garraway, Mark A Rubin, Francesca Demichelis
Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer
published pages: 298-305, ISSN: 1078-8956, DOI: 10.1038/nm.4045
Nature Medicine 22/3 2019-06-06
2017 Ping Mu, Zeda Zhang, Matteo Benelli, Wouter R. Karthaus, Elizabeth Hoover, Chi-Chao Chen, John Wongvipat, Sheng-Yu Ku, Dong Gao, Zhen Cao, Neel Shah, Elizabeth J. Adams, Wassim Abida, Philip A. Watson, Davide Prandi, Chun-Hao Huang, Elisa de Stanchina, Scott W. Lowe, Leigh Ellis, Himisha Beltran, Mark A. Rubin, David W. Goodrich, Francesca Demichelis, Charles L. Sawyers
SOX2 promotes lineage plasticity and antiandrogen resistance in TP53 - and RB1 -deficient prostate cancer
published pages: 84-88, ISSN: 0036-8075, DOI: 10.1126/science.aah4307
Science 355/6320 2019-06-06
2016 Bishoy M Faltas, Davide Prandi, Scott T Tagawa, Ana M Molina, David M Nanus, Cora Sternberg, Jonathan Rosenberg, Juan Miguel Mosquera, Brian Robinson, Olivier Elemento, Andrea Sboner, Himisha Beltran, Francesca Demichelis, Mark A Rubin
Clonal evolution of chemotherapy-resistant urothelial carcinoma
published pages: 1490-1499, ISSN: 1061-4036, DOI: 10.1038/ng.3692
Nature Genetics 48/12 2019-06-06
2017 Gianluca Petris, Antonio Casini, Claudia Montagna, Francesca Lorenzin, Davide Prandi, Alessandro Romanel, Jacopo Zasso, Luciano Conti, Francesca Demichelis, Anna Cereseto
Hit and go CAS9 delivered through a lentiviral based self-limiting circuit
published pages: 15334, ISSN: 2041-1723, DOI: 10.1038/ncomms15334
Nature Communications 8 2019-06-06

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