Project description
Novel targets for treating uveal melanoma
Uveal melanoma is a rare yet deadly primary cancer of the eye in adults associated with mutations in two transmembrane G protein-coupled receptors. The malignancy emerges in melanocytes in the ocular region. Although surgical resection and radiation are used to treat local disease, half of the patients develop metastases and die within one year. The scope of the EU-funded NECESSITY project is to identify novel targets for therapeutic intervention. Researchers will study the signalling pathways in uveal melanoma cells and identify molecules that inhibit cell growth and initiate apoptosis. Results will provide fundamental information on an unmet medical need, hoping to improve the clinical outcome of patients with uveal melanoma.
Objective
G protein-coupled receptors (GPCRs) represent the largest family of cell surface proteins involved in signal transmission. Nearly 30% of human cancers harbor mutations in GPCRs/G proteins. Activating mutations in GNAQ and GNA11 have been discovered in 90% of Uveal Melanoma (UM).UM is the most common primary cancer of the eye in adults and to date there are no effective treatments. 50% of UM patients develop metastatic disease, which is refractory to current chemotherapies leading to patient death within a year. Prolonged Gaq signaling leads to the activation of YAP, a transcriptional co-activator regulated, necessary for UM growth. GNAQ stimulates YAP through FAK. Inhibition of FAK reduces UM growth,leading FAK to be a potential therapeutic target for UM. In UM, the particular Gαq–regulated pathways that when overactive can render FAK inhibitor(FAKi) ineffective, as well as what feedback mechanisms should be targeted to optimize therapeutic responses to FAKi are still unknown. I will use a panel of GNAQ-driven UM cells and perform a genetic screen using the Cancer Signaling Toolkit to discover molecular determinants of sensitivity or resistance to FAK inhibition. Signaling candidates and screening hits discovered will be prioritized and their biological impact in UM growth and FAKi sensitivity will be evaluated. To increase FAKi activity and reduce therapy resistance, I will also investigate whether co-targeting candidate GNAQ-effector and FAKi resistance pathways will synergize with FAKi, resulting in UM cell death. Finally,I will explore the mechanism of UM cell death by co-targeting. My studies will reveal new targeted(precision) strategies for multiple Gαq-driven pathological conditions in cancer The project will be supervised by Dr. Gutikind and Dr.Martini two experts in GPRC/G proteins. Through this work, I aim to broaden my scientific expertise (including technical and transferable skills) and to establish myself as an independent researcher in cancer biology
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine oncology skin cancer melanoma
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics mutation
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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) H2020-MSCA-IF-2020
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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.
56126 PISA
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.