Project description
Novel drugs to overcome resistance to targeted therapy in melanoma treatment
Targeted therapies use drugs that reduce the growth and spread of cancer cells via the inhibition of specific proteins or pathways. Recent studies have shown that melanoma targeted therapies based on BRAF and MEK inhibitors increase reactive oxygen species in melanoma, resulting in activation of antioxidant mechanisms that keep tumour cellular redox state below a deadly threshold. The removal of antioxidants could be exploited for therapeutic benefits. Previously, the research team of the EU-funded MELASTOP project discovered that the mevalonate metabolic pathways have antioxidant properties and are critical regulators of oxidative stress in pathological conditions, including melanoma progression. Now, the project aims to validate the repositioning of the existing mevalonate pathway inhibitors as novel therapeutic drugs to treat melanoma resistance.
Objective
Melanoma is the most aggressive skin tumor, extremely difficult to treat and with high mortality rate. Overcoming reduced sensitivity and acquired resistance to targeted therapy is a major goal of current melanoma research. Therefore, there is an urgent need for development of novel drugs that can cure and prolong the survival of melanoma patients. Molecular targeted therapy by using a drug that reduces the growth and spread of cancer cells via inhibition of specific protein or pathway is a milestone of precise medicine and treatment. Recent observations demonstrate that BRAF and MEK inhibitors induce increased reactive oxygen species (ROS) in melanoma and as a consequence tumor cells activate adaptive antioxidant mechanisms to keep their cellular redox state below a deadly threshold. Thus, it has been proposed that removal of antioxidant could be exploited for therapeutic benefits. In our ERC Consolidator grant RENDOX we have characterized the mevalonate metabolic pathway and discovered that this metabolic pathway as well as its enzyme, UBIAD1, have antioxidant properties and are critical caretakers of oxidative stress and ferroptosis in pathological conditions, such as melanoma progression. The MELASTOP project is grounded on the validation and repositioning of pre-existing inhibitors, such as statins and parabens derivatives (UBIAD1i) as novel therapeutic drugs to treat melanoma resistance, which represents an extraordinary opportunity to improve the current limitation. The current ERC PoC proposal aims at lead optimization, preclinical validation, IPR positioning, marker assessment and other commercial activities including go to market strategy and dialogue with potential collaborators of these mevalonate and UBIAD1 inhibitors. We envision that this PoC represents a unique medical and commercial opportunity to treat and cure BRAF-resistant melanoma patients in urgent need of new treatment options.
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.
- social sciences sociology demography mortality
- medical and health sciences clinical medicine oncology skin cancer melanoma
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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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-POC - Proof of Concept 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-2020-PoC
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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.
35122 PADOVA
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.