Preclinical models in oncological pharmacology: limits and advantages

A wide range of experimental tumor models, each with distinct advantages and disadvantages, is nowadays available. Due to the inherent differences in their complexity and functionality, the choice of the model is usually dependent on the application. Thus, to advance specific knowledge, one has to choose and use appropriate models, which complexity is largely dependent on the hypotheses to test, that is on the objectives. Whatever the model chosen, the complexity of cancer is such that none of them will be able to fully represent it. In vitro tumor models have provided important tools for cancer research and still serve as low-cost screening platforms for drugs. The improved understanding of cancer as "organ system" has pushed for increased accuracy and physiological relevance of in vitro tumor models that have in parallel increased in complexity, diversifying their output parameters as they progressed in view to recapitulate the most critical aspects such as the dimensionality of cell cultures (2D versus 3D), the mechanical stimuli, the multicellular interactions, the immune interactions and the soluble signaling. Animal models represent the in vivo counterpart to cell lines and are commonly used for studies during the preclinical investigation of cancer therapy to determine the efficacy and safety of novel drugs. They are super to in vitro models in terms of physiological relevance offering imitation of parental tumors and a heterogeneous microenvironment as part of an interacting complex biochemical system. In the present review we describe advantages and limits of major preclinical models used in Oncological Pharmacology.