Scientific EMU: acquisition of an ex vivo model analysis platform for precision oncology

Abstract

Functional precision oncology is a very young area of medicine, whose main goal is to use patient derived cells as models for predicting response to therapy. These models can be characterized genetically, through gene expression profile and activation of biological pathways. With this information, cells can be challenged with different drug regimens to provide personalized and immediately translatable information to guide patient's therapy. Cells can be grown either using classical methodologies such as monolayer cultures or in three-dimensional structures such as organoids. A clear advantage of this type of approach is that the use of cells derived directly from patients allows for the unpredictability of cancer treatment observed in numerous situations to be mimicked by such cultures. Currently, precision oncology has focused on describing individual tumor genomic characteristics to guide therapies. Such strategies have brought a great advance in oncological treatment with significant improvements in survival, especially for some types of tumors. However, even for patients in whose tumors a "targetable" change is detected, not all patients experience benefit from the chosen treatment. Therefore, there is a need to create strategies that increase the number of patients benefiting from precision oncology. Our proposal is to generate a platform that allows for the comprehensive characterization of tumor models and development of functional tests capable of identifying vulnerabilities and predicting therapy response. The equipment requested in this proposal is aligned to this goal, creating a complete facility for the genetic and functional characterization of ex vivo models and carrying out personalized pre-clinical drug sensitivity assays. The team's expertise in genetics and cell biology meets the need for the requested equipment, in order to conduct a strategy that can improve clinical outcomes, reduce discomfort and adverse effects of ineffective therapies, in addition to reducing costs. In a complementary way, the platform will also benefit projects that evaluate other functional and mechanistic aspects of cancer, such as the study models of HPV, glioblastomas and hereditary tumors. (AU)