Three-dimensional culture systems

3D cell cultures appear in many different self-made and commercially available facets. A common denominator for some of them is that they enable cell growth in a more physiological environment than conventional 2D cell cultures. Unfortunately, validation of their suitability to do so and to fit to a particular scientific question is mostly missing. In this teaching lecture I will discuss validation strategies and data of comparative analyses between 2D, 3D and tumor xenografts of various processes such as signal transduction, DNA repair and others. Based on our long-standing experience, a large variety of endpoints can be determined and many methods can be conducted in 3D cell cultures. While this is sometimes not as easy as in 2D and also requires a bit more financial invest, the generated data reflect cell behavior in-vivo and thus have a higher clinically relevance. Further, we are able to address specific tumor features in detail. For example, malignant tumors show great genetic/epigenetic and morphological/cell biological heterogeneity. Another important point is the sparing of animal experiments based on our broad knowledge that human (patho)physiology is significantly different from mice (or other species). Many decades of in-vivo research have demonstrated that only a negligible proportion of therapeutic approaches could be translated from rodents to humans. In conclusion, 3D cell culture models can elegantly support our efforts to gain more knowledge for precision cancer medicine as they present powerful tools for generating more clinically relevant information. A broader implementation of the 3D methodology is likely to underscore our efforts to better understand tumor and normal cell radiation responses and foster identification of most critical cancer targets.