Objective
HER2 is a membrane receptor tyrosine kinase overexpressed in 30% of breast tumors and results in an aggressive clinical course. Anti-HER2 therapies including monoclonal antibodies (trastuzumab) and small-molecule tyrosine kinase inhibitors (lapatinib) are active and have improved survival of patients with HER2 overexpressing breast cancer. However, the emergence of primary or acquired resistance to these agents limits their efficacy. We have previously identified mechanisms of resistance to anti-HER2 therapies such as the co-expression of a truncated form of HER2 that correlates with trastuzumab resistance or the presence of downstream oncogenic mutations of PI3K or PTEN loss that result in resistance to lapatinib . Not surprisingly, PI3K/mTOR inhibitors overcome lapatinib resistance in the later example. Building on our results to date, this proposal is aimed at identifying novel mechanisms of resistance to anti-HER2 agents and to devise therapeutic strategies to revert it. To uncover such mechanisms, we have generated cancer cells with acquired resistance to lapatinib or trastuzumab by continuous exposure to increasing concentrations of these agents. We will perform genome wide screens, including shRNA libraries, gene expression and SNPs arrays, to discover candidate genes responsible for decreased sensitivity to anti-HER2 agents. To overcome anti-HER2 therapy resistance we will study several therapeutic strategies, such as combinations of different anti-HER2 compounds and the use of alternative agents targeting downstream/parallel pathways. Among the novel targeted therapies, we plan to study the use of PI3K, Akt, CDK2 and Hsp90 inhibitors, for which we will also start resistance-screens. It is anticipated that any promising preclinical leads will stimulate trial design and conduct for subsequent evaluation and confirmation in the clinic.
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 breast cancer
- natural sciences biological sciences genetics mutation
- natural sciences biological sciences genetics genomes
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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.
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.
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.
ERC-2009-AdG
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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.
Host institution
08035 Barcelona
Spain
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.