Project description DEENESFRITPL Molecular insight into drug resistance mechanisms in breast cancer Breast cancer ranks as one of the most prevalent forms of cancer in women today. Despite advances in targeted therapies, nearly 25 % of patients do not respond to treatment, or they develop drug resistance. The scope of the EU-funded NOSCAR project is to investigate the mechanisms of resistance to therapy. Scientists will focus on the oncogenic Ras/Erk and PI3K/Akt/mTOR signalling pathways known for their role in cell survival, proliferation, motility and metabolism. They will assess how these pathways are rewired in the presence of clinically relevant breast cancer mutations or following drug treatment. The project's results have the potential to identify novel targets for treating breast cancer in the future. Show the project objective Hide the project objective Objective Despite significant progress in drug therapies for breast cancer, about one fourth of patients still do not survive the disease. Modern, targeted therapies have been proposed to cure the more advanced and aggressive cases of breast cancer. However, non-genetic and genetic mechanisms of drug resistance currently limit the promise of targeted therapy. NOSCAR aims to define the oncogenic Ras/Erk and PI3K/Akt signalling states relevant to breast cancer oncogenic mutations, and delineate the mechanisms which enable development of cancer resistance to targeted therapies.NOSCAR’s objectives are: Using a quantitative cell biology framework that combines a multiplexed biosensor system that reports on Erk/Akt dynamics at single cell level, computer vision, and statistical modelling, I will:(1) produce an atlas of single-cell Erk/Akt dynamic signalling patterns that are associated with a compendium of clinically-relevant breast cancer mutations;(2) measure the signalling states in cells perturbed with clinically-relevant drugs that target different components of the Ras/Erk and PI3K/Akt pathways to evaluate how the oncogenic signalling network is rewired by drug treatment;(3) measure signalling dynamics in 3D spheroid cultures and patient-derived organoids to explore how a self-organizing cellular ecosystem can spatially control signalling at the single cell level to locally control fate decisions, and how the latter process is compromised by an oncogenic mutation.This will provide new insights about tumor heterogeneity and signaling network structures that confer robustness against drug perturbations. We expect to identify vulnerabilities that might be efficiently targeted by drug combinations, providing new avenues to treat breast cancer.The planned research together with training and mentoring that I will receive thanks to the fellowship, will enable to successfully restart my career in research and will significantly benefit my further academic career prospects. Fields of science natural sciencescomputer and information sciencesartificial intelligencecomputer visionnatural sciencesbiological sciencescell biologymedical and health sciencesbasic medicinepharmacology and pharmacydrug resistancemedical and health sciencesclinical medicineoncologybreast cancernatural sciencesbiological sciencesgeneticsmutation Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2019 - Individual Fellowships Call for proposal H2020-MSCA-IF-2019 See other projects for this call Funding Scheme MSCA-IF-EF-CAR - CAR – Career Restart panel Coordinator UNIVERSITAET BERN Net EU contribution € 304 724,16 Address Hochschulstrasse 6 3012 Bern Switzerland See on map Region Schweiz/Suisse/Svizzera Espace Mittelland Bern / Berne Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
