Copyright: © Twan Lammers Challenges in Tumor-Targeted Drug Delivery (left) and strategy of the RTG and positioning of the 12 projects witin three main application fields (right).

To enforce breakthroughs in the performance and clinical translation of tumor-targeted DDS, cutting edge research at the interfaces of tumor biology, chemical engineering and clinical medicine has to be brought together in a systematic manner, with strong and intimate collaborations. Indeed, we believe these three disciplins form the main vantage points from which the field should be viewed and from which approaches should be taken to move towards a better understanding, performance and translation of tumor-targeted DDS. In our RTG, these vantage points will serve as the three cornerstones that help construct our research network and in between which the research projects will be structured and organized.

• From the vantage point tumor biology, it is important to better understand the behavior of DDS in the heterogeneous tumor microenvironment, and to investigate how these environments vary between primary tumors and metastases. This enables a more rational choice of DDS or targeting strategy for a specific cancer and even for an invidividual patient. It furthermore serves as a basis for approaches to pharmacologically or physically modulate the tumor vasculature and the microenvironment to enable more efficient drug delivery, and to identify new strategies for DDS-based immuno-chemotherapy combinations.

• From the vantage point chemical engineering, carrier materials have to be developed that consider the molecular and pathophysiological properties of tumors and their heterogeneity, e.g. via radiolabelling to enable patient selection or via designing DDS that respond to different and changing microenvironments. Furthermore, carriers with improved penetration behavior, controlled release kinetics and the ability for multi-drug loading are needed. Production and upscaling processes will be controlled by establishing techniques such as continuous-flow manufacturing.

• From the vantage point clinical medicine, it is important to understand the clinical needs, the diagnostic and theranostic procedures, and the differences between preclinical and clinical disease models. Research efforts should be taken to develop preclinical tumor models and treatment scenarios that closely match the envisioned clinical scenario. Furthermore, for bringing new DDS into patients, knowledge must be acquired and tools developed ensuring reliable production and quality control of DDS. Expertise in and infrastructure for conducting clinical phase 0 to 2 trials are further prerequisites. In addition, the successful translation of DDS may strongly depend on patient preselection and therapy monitoring requirering non-invasive imaging tools and on the choice of ideal drug combinations as well as on the support of pharmacologicial therapies by physical interventions. In this context, drug repurposing in combination therapies can be a highly promising approach that provides a fast and easy clinical entry.