Obiettivo Current chemotherapeutic agents are potent enough to kill cancer cells. Nonetheless, failure of standard chemotherapies for many cancer types (e.g. pancreatic and breast cancers) is primarily attributed to these agents never reaching cancer cells in amounts sufficient for complete cure. In solid tumours, blood vessels are often compressed, drastically reducing perfusion, thus resulting in insufficient drug delivery. Vessel compression is a consequence of mechanical stresses accumulated within the tumour during progression. Alleviation of these stresses has the potential to reopen compressed vessels and improve tumour perfusion. Here, the applicant proposes to test the hypothesis that judicious depletion of stromal cells, namely the cancer-associated fibroblasts (CAFs), has the potential to alleviate stress levels in highly desmoplastic and hypoperfused tumours and, thus, enhance chemotherapy. To explore this hypothesis, a combination of cutting-edge computational and experimental techniques will be employed. Specifically, a structure-based biomechanical model will be developed to analyse the contribution of CAFs to the generation and transmission of forces within a tumour. Subsequently, in vivo studies will be performed in mice to validate model predictions and identify the degree of CAF depletion that optimizes the efficacy of treatment. Successful completion of the proposed research will reveal the role of CAFs on the biomechanical behaviour of tumours and contribute to developing a therapeutic strategy for treatment of hypovascular tumours. Therefore, the proposal negotiates a subject of considerable importance for European society and beyond. Furthermore, the proposed research and training will establish a bidirectional transfer of skills where the applicant’s expertise in cell mechanics will be complemented by the Host’s in cancer biophysics, thus enhancing the applicant’s scientific potential and professional maturity, and promoting European research. Campo scientifico medical and health sciencesmedical biotechnologygenetic engineeringmedical and health sciencesmedical biotechnologynanomedicinemedical and health sciencesclinical medicineoncologybreast cancermedical and health sciencesclinical medicineoncologypancreatic cancernatural sciencesmathematicsapplied mathematicsmathematical model Programma(i) 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 Argomento(i) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Invito a presentare proposte H2020-MSCA-IF-2014 Vedi altri progetti per questo bando Meccanismo di finanziamento MSCA-IF-EF-ST - Standard EF Coordinatore UNIVERSITY OF CYPRUS Contribution nette de l'UE € 151 648,80 Indirizzo AVENUE PANEPISTIMIOU 2109 AGLANTZI 1678 Nicosia Cipro Mostra sulla mappa Regione Κύπρος Κύπρος Κύπρος Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 151 648,80