A multi-scale model that has a vascular layer, a cellular layer and an intracellular layer. With this model it is Necrostatin-1MedChemExpress Necrostatin-1 possible to get detailed spatio-temporal information about the tumor and the healthy tissue. In general three results are possible with the model; the tumor is eliminated, the tumor continues grow, or an oscillation. It is possible to combine different treatments in one model. The model of de Pillis et al. [63] based on a previous model [64] combines different treatments and shows that if the chemotherapy is stopped a system with a undetectable tumor can return to a high tumor state. The combination of different treatments is one possibility to eliminate the patient’s tumor. Jackson et al. [65] introduced two different types of cells and investigated the tumors response to different chemotherapeutic strategies. It was possible to estimate the largest size of a tumor that can be eradicated by a bolus injection. With only one cell population the results of bolus and continues drug were similar. With two populations, one of them drug resistant, the continuous infusion increased the time to cure. This indicates that it is important to tailor treatment strategies.Clinical observationMathematical modelExperiments/ clinical studiesHypothesesSimulationsExperimental designNew knowledgeFigure 1 Cycles of experiments and modeling for gaining new knowledge. Experiments and clinical studies are closely coupled with mathematical modeling and simulations and require multiple cycles of iterations.Gallasch et al. Journal of Clinical Bioinformatics 2013, 3:23 http://www.jclinbioinformatics.com/content/3/1/Page 5 ofAnother interesting aspect is the use of growth factors in the model from Panetta and Adam [66]. They showed that the use of growth factors in their model increases the cell killing up to 20 . Based on the model of Anderson and Chaplain [27] McDougall [29] developed a model where the blood viscosity, pressure drop and mean capillary radii can be varied of the surrounding vessels of a solid tumor can be analyzed. The model shows that if there are highly interconnected vessels around the tumor there is a low drug delivery to the tumor itself. It shows that it is important to consider the vasculature around the tumor to find the optimal chemotherapy strategy. The strategy of chemotherapy in combination with other treatments is being increasingly used. Powathil addressed this in recent publications [67-69] and showed ways to simulate and improve protocols of chemotherapy. It was demonstrated that the cytotoxic effect is dependent on many factors like timing of the drug delivery, time delay between the doses, heterogeneities of the cell cycle, the spatial distribution of the tumor and the surrounding microenvironment. It is noteworthy that these issues have been also investigated in older studies, e.g. using models of phase-specificity of chemotherapeutic drugs published in the 1990s [70]. In this section different methods were shown to model chemotherapy and effects that can lead to a better treatment strategy. Most PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28404814 targeted cancer therapies use monoclonal antibodies directed against tumor-specific surface proteins or small-molecule drugs against intracellular targets (e.g. tyrosin kinases) [71]. Billy et al. [72] developed a model that simulates a treatment on the angiogenesis of tumors by gene therapy. The gene therapy is delivered by adenoviruses and influences, the antagonist of vascular endothelial growth factor, endostatin. The s.