Dynamic Culture Systems and 3D Interfaces Models for Cancer Drugs Testing.

The mass use of biological agents for pharmaceutical purposes started with the development and distribution of vaccines, followed by the industrial production of antibiotics. The use of dynamic systems, such as bioreactors, had been already applied in the food industry in fermentation processes and started being used for the development of pharmaceutical agents from this point on. In the last decades, the use of bioreactors and microfluidic systems has been expanded in different fields. The emergence of the tissue engineering led to the development of in vitro models cultured in dynamic systems. This is particularly relevant considering the urgent reduction of the total dependence on animal disease models that is undermining the development of novel drugs, using alternatively human-based models to make the drug discovery process more reliable. The failure out coming from animal models has been more prevalent in certain types of cancer, such as glioblastoma multiform and in high-grade metastatic cancers like bone metastasis of breast or prostatic cancer. The difficulty in obtaining novel drugs for these purposes is mostly linked to the barriers around the tumors, which these bioactive molecules have to overcome to become effective. For that reason, the individualized study of each interface is paramount and is only realistic once applying human-based samples (e.g. cells or tissues) in three-dimensions for in vitro modeling under dynamic conditions. In this chapter, the most recent approaches to model these interfaces in 3D systems will be explored, highlighting their major contributions to the field. In this section, these systems' impact on increased knowledge in relevant aspects of cancer aggressiveness as invasive or motile cellular capacity, or even resistance to chemotherapeutic agents will have particular focus. The last section of this chapter will focus on the integration of the tumor interfaces in dynamic systems, particularly its application on high-throughput drug screening. The industrial translation of such platforms will be discussed, as well as the main upcoming challenges and future perspectives.