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Synthetic Lethal Phenotype Identification through Cancer Evolution Analysis

Total Cost €


EC-Contrib. €






 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.

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

Project "SPICE" data sheet

The following table provides information about the project.


Organization address
address: VIA CALEPINA 14
city: TRENTO
postcode: 38122

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
 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


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


 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.


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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