Project description DEENESFRITPL Pyruvate metabolism and extracellular matrix remodelling in the targeting of metastatic cancer Metastases, or secondary tumours, are the leading cause of cancer deaths. Many breast cancer patients get the diagnosis when cancer cells have already disseminated to distant organs. Extracellular matrix (ECM) remodelling in the metastatic niche is essential for disseminated breast cancer cells to promote the growth of the new metastasis. The host laboratory has recently discovered that the nutrient pyruvate metabolically drives breast cancer cells to remodel the ECM. The EU-funded MetaTarGet project is capitalising on this discovery to explore the potential targeting of ECM remodelling in metastasis. The research will focus on pyruvate metabolism as an ECM remodelling regulator and a novel therapeutic strategy to target metastatic outgrowth. Show the project objective Hide the project objective Objective Distant metastases, i.e. secondary tumors, are the leading cause of cancer deaths. Many patients (especially with breast cancer) are diagnosed when cancer cells have already disseminated to distant organs. Thus, it is of profound importance to prevent the metastatic outgrowth of these disseminated cancer cells into secondary tumors. The ability to remodel the extracellular matrix (ECM) of the metastatic niche is essential for disseminated breast cancer cells to promote their own metastatic outgrowth. This process is to date believed to be transcriptionally regulated. However, the Fendt laboratory has discovered that the nutrient pyruvate metabolically drives ECM remodeling by breast cancer cells. In my project, I will build on this discovery and explore how to target ECM remodeling in metastatic outgrowth. First, I will determine the interaction between the discovered metabolic and the known transcriptional regulation of ECM remodeling. Secondly, I will translate this novel finding into therapeutic potential by defining how to selectively target it, thereby impairing metastatic outgrowth in the lung environment. Thirdly, I will define how the metastatic site and the cancer cell origin affect the discovered metabolic regulation of ECM remodeling, and thus metastatic outgrowth. To address these aims, I will use metabolomics, 13C tracer analysis, genetic engineering and nanotechnology-based drug-delivery in breast cancer 3D cultures and mouse models. With MetaTarGet, I will deliver (i) a mechanistic understanding of pyruvate metabolism as a regulator of ECM remodeling, and (ii) a novel therapeutic strategy to target metastatic outgrowth. This project will allow me to bridge my nanotechnology-based drug-delivery knowledge with the expertise of the Fendt laboratory in metastasis metabolism. Consequently, I will strengthen my research competences and enhance my personal research profile. Fields of science medical and health sciencesmedical biotechnologygenetic engineeringmedical and health sciencesclinical medicineoncologybreast cancer 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-2018 - Individual Fellowships Call for proposal H2020-MSCA-IF-2018 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator VIB VZW Net EU contribution € 166 320,00 Address SUZANNE TASSIERSTRAAT 1 9052 ZWIJNAARDE - GENT Belgium See on map Region Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent Activity type Research Organisations 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 Total cost € 166 320,00
