Objective "Cancer is a devastating disease affecting 1 in 3 people in their lifetime. The incidence is rising because of our aging population and causes a huge economic impact on our society because of hospitalization and lost productivity. Radiotherapy alone or in combination with surgery and/or chemotherapy is used in ~50% of all patients and uses ionizing radiation to induce DNA breaks that are lethal to cells. While significant progress has been made, radiotherapy is often limited because of side-effects in normal tissues and tumor control often fails because of resistance and metastases. Novel treatment paradigms are urgently needed. Among the key classical biological factors that determine radiation response in normal and tumor cells are the 4R; Reoxygenation, Repopulation, Redistribution and Repair. They are determined by intrinsic (genetic) as well as extrinsic factors from the tumor microenvironment and underlie tumor heterogeneity a hallmark of cancers and a decisive factor in clinical response. Yet, standard cancer treatments are largely based on the flawed assumption that tumors are homogenous within and between patients. We hypothesized that NOTCH signaling and tumor hypoxia cause tumor heterogeneity and are tumor selective therapeutic targets. First we will study key biological mechanisms that determine intra tumor heterogeneity, second we will establish their role in therapy response and third we will exploit this knowledge to enhance radiotherapy and provide proof of concept of a highly innovative approach to selectively activate cancer therapeutics targeting the NOTCH stem cell pathway in therapy resistant tumor cells without adverse effects in normal tissues.DIRECT interrogates the molecular details of key cancer therapy response parameters providing opportunities for the next generation of tumor cell specific treatments that improve disease outcome." Fields of science medical and health sciencesclinical medicinesurgerynatural sciencesphysical sciencesnuclear physicssocial scienceseconomics and businesseconomicsproduction economicsproductivitymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineoncology Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-CG-2013-LS7 - ERC Consolidator Grant - Diagnostic Tools, Therapies and Public Health Call for proposal ERC-2013-CoG See other projects for this call Funding Scheme ERC-CG - ERC Consolidator Grants Host institution UNIVERSITEIT MAASTRICHT EU contribution € 1 541 776,80 Address MINDERBROEDERSBERG 4 6200 MD Maastricht Netherlands See on map Region Zuid-Nederland Limburg (NL) Zuid-Limburg Activity type Higher or Secondary Education Establishments Administrative Contact Judith Doomen (Ms.) Principal investigator Marc Antoine Gijsbert Gilles Vooijs (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all UNIVERSITEIT MAASTRICHT Netherlands EU contribution € 1 541 776,80 Address MINDERBROEDERSBERG 4 6200 MD Maastricht See on map Region Zuid-Nederland Limburg (NL) Zuid-Limburg Activity type Higher or Secondary Education Establishments Administrative Contact Judith Doomen (Ms.) Principal investigator Marc Antoine Gijsbert Gilles Vooijs (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data THE UNIVERSITY OF AUCKLAND New Zealand EU contribution € 288 733,20 Address PRINCES STREET 24 1010 Auckland See on map Activity type Higher or Secondary Education Establishments Administrative Contact Julia Zhu (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data