Project description
The impact of genetic background on response to chemotherapy
Cells ensure genomic stability through various mechanisms that repair DNA damage induced by drugs or ultraviolet radiation. One of these, global-genome nucleotide excision repair (GG-NER) detects bulky DNA lesions anywhere in the genome independently of transcription and repairs them. The EU-funded REAP project is interested to understand how mutations in the GG-NER pathway affect the outcome of platinum drugs such as oxaliplatin and cisplatin. Researchers will investigate the mutations that affect this differential recognition of platinum lesions by GG-NER. The generated insight will improve the outcome of existing chemotherapy protocols through genetic profiling of cancer patients.
Objective
DNA damage-inducing platinum drugs, such as oxaliplatin and cisplatin, are used to treat about half of all patients receiving chemotherapy. Although potentially very efficient, many patients develop resistance for yet unrecognized reasons. Better understanding of the DNA damage response (DDR) to platinum-DNA lesions is therefore much needed for improving treatment outcomes.
By performing DDR-dedicated CRISPR/Cas9 knockout screens, the applicant has shown that some cancer cells deficient in the major repair of bulky DNA lesions, global-genome nucleotide excision repair (GG-NER), are insensitive to oxaliplatin but sensitive to cisplatin. This striking difference remains as of yet unreported, but might explain differential responses of tumors to drugs. The aim of this proposal is to understand why GG-NER is unable to repair oxaliplatin lesions in particular genetic backgrounds. To do so, unbiased identification of genes differently mutated or expressed in oxaliplatin-sensitive versus insensitive cells will be followed by validation and in-depth functional characterization of identified targets. The ambition is to extrapolate experimental observations to translational knowledge. Validated targets will be studied in patient-derived tumor tissues as compared to nonmalignant tissues and related to patients’ treatment responses. Identification of genetic factors that regulate platinum lesions recognition by GG-NER will contribute to the understanding of molecular principles of platinum drugs cytotoxicity and might thus have considerable benefit on current cancer treatment schemes.
The novelty of the pilot data, the unique multidisciplinary design of the project, the use of state-of-the-art molecular techniques and a collaboration with multiple European experts will ensure high scientific impact. Both, the applicant and the host will greatly benefit from the vital knowledge transfer. This project follows the European Union's commitment to cancer research.
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.
- natural sciences biological sciences genetics DNA
- natural sciences chemical sciences inorganic chemistry transition metals
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics nucleotides
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
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.
-
H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
See all projects funded under this programme -
H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
See all projects funded under this programme
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-ST - Standard EF
See all projects funded under this funding scheme
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
See all projects funded under this callCoordinator
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.
1090 Wien
Austria
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.