Abstract

Increased Physiological Relevance of Tumor Cells in Pre-clinical Research: The Pathway for Earlier and Higher Prediction of Drug Efficacy

Vitor Espirito Santo, Researcher, Universidade Nove de Lisboa

Tumor microenvironment has been increasingly reported to influence the response of tumor cells to therapeutics. Therefore, the design of in vitro cell models with improved features of tumor niche can contribute to establish a more predictive tumor model, thus playing a pivotal role in pre-clinical research and drug discovery. In this talk, I will give an overview on our contributions in the field, namely on the establishment of 3D culture systems in which we combine alginate microencapsulation with agitation-based culture systems, to recapitulate key aspects of the tumor microenvironment and disease progression. With our strategy, we can generate tumor microtissues composed of tumor spheroids, fibroblasts and immune cells that can be cultured up to months. We have successfully applied this strategy to different pathologies, such as breast and lung cancer. We could detect accumulation of extracellular matrix proteins and secretion of cytokines that in certain cases could lead to phenotypic alterations of the tumor cells more characteristic of advanced tumors. The plasticity of the model was also demonstrated by the incorporation of immune cells, with gradual polarization of monocytes towards activated type 2. This model constitutes a new and versatile tool to depict the role of tumor-stromal cross-talk in drug response and tumor evolution and is also currently being used to patient-derived material.