Project description
Kinase inhibitors as a therapy against oesophageal cancer
Oesophageal squamous cell carcinoma (eSCC) presents with various genetic alterations that affect the activity of kinase enzymes which are involved in signalling pathways, the cell cycle or cell proliferation. However, heterogeneity associated with kinase deregulation impedes the development of a uniform anti-kinase therapy for eSCC. To support the design of novel therapeutic interventions, scientists of the EU-funded Kinaddict project will employ omics approaches to investigate how eSCC responds to kinase inhibitors. Insight into the molecular mechanisms of these responses will lead to biomarkers indicative of treatment outcome as well as combinatorial therapies.
Objective
In decades, the 5-year survival rate of several cancers has barely been improved and the esophageal squamous cell carcinoma (eSCC) is not different with a rate around 25%. In order to increase the survival, chemoradiotherapy prior surgery has become the reference for eSCC despite still a high mortality. eSCC tumors harbor a variety of genetic alterations directly or indirectly affecting the activity of kinases involved in signaling pathways, the cell cycle or the proliferation. Evidence on how eSCC tumors are addicted to such oncogenic alterations remains missing to evaluate alternative treatment modalities. The heterogeneity of eSCC tumors presenting deregulations of diverse constellations of kinases has rendered difficult the development of a unique therapeutic strategy similar to prior successes targeting EGFR or BCR-ABL. However, as the CDK4 activity lies downstream from most of the oncogenic deregulations of signalling pathways, it has been proposed to represent the therapeutic target of choice, confirmed by the first approval by the FDA/EMA of 3 CDK4/6 inhibitors to treat ER+ breast cancer. Despite this, not all tumors respond to CDK4 inhibition and long-term treatment triggers escape mechanisms. In this context, the main aim of the present proposal consists to preclinically evaluate if and how eSCC respond to inhibitors targeting kinases with an altered activity using a multi-omics approach. In this cancer, we will (1) identify the kinases with a deregulated activity associated to different genetic landscapes and determine the addiction of eSCC to their activity, (2) characterize the sensitivity of eSCC tumors to CDK4 inhibition and decipher their molecular response for effective combined targeted therapy, and (3) experimentally define the treatment modalities of eSCC in mouse models. The results will provide a strong basis to extend the study with clinicians to human tumors to determine biomarkers of responsiveness to efficient alternative therapy.
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 surgery
- medical and health sciences clinical medicine oncology skin cancer squamous cell carcinoma
- medical and health sciences clinical medicine oncology breast cancer
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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.1.3. - 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-EF-RI - RI – Reintegration panel
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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-2018
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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.
1050 Bruxelles / Brussel
Belgium
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.