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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences basic medicine pharmacology and pharmacy drug discovery
- medical and health sciences clinical medicine oncology prostate cancer
- medical and health sciences clinical medicine oncology bladder cancer
- medical and health sciences medical biotechnology genetic engineering gene therapy
- natural sciences biological sciences genetics DNA
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
ERC-COG - Consolidator Grant
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2014-CoG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
38122 Trento
Italy
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.