title: Drug screening in 3D in vitro tumor models: overcoming current pitfalls of efficacy read-outs.
abstract: There is cumulating evidence that in vitro 3D tumor models with increased physiological relevance can improve the predictive value of pre-clinical research and ultimately contribute to achieve decisions earlier during the development of cancer-targeted therapies. Due to the role of tumor microenvironment in the response of tumor cells to therapeutics, the incorporation of different elements of the tumor niche on cell model design is expected to contribute to the establishment of more predictive in vitro tumor models. This review is focused on the several challenges and adjustments that the field of oncology research is facing to translate these advanced tumor cells models to drug discovery, taking advantage of the progress on culture technologies, imaging platforms, high throughput and automated systems. The choice of 3D cell model, the experimental design, choice of read-outs and interpretation of data obtained from 3D cell models are critical aspects when considering their implementation in drug discovery. In this review, we foresee some of these aspects and depict the potential directions of pre-clinical oncology drug discovery towards improved prediction of drug efficacy.
authors.affiliation: iBET, Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal.|Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: Vítor E
authors.initials: VE
authors.lastname: Santo
authors.affiliation: iBET, Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal.|Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: Sofia P
authors.initials: SP
authors.lastname: Rebelo
authors.affiliation: iBET, Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal.|Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: Marta F
authors.initials: MF
authors.lastname: Estrada
authors.affiliation: iBET, Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal.|Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: Paula M
authors.initials: PM
authors.lastname: Alves
authors.affiliation: Abbvie, North Chicago, IL, USA.
authors.forename: Erwin
authors.initials: E
authors.lastname: Boghaert
authors.affiliation: iBET, Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal.|Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Brito
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D055808:Drug Discovery; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D006801:Humans; D017154:Stromal Cells / Q000166:cytology / Q000473:pathology; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents
keywords: 3D cell models; Cancer; Drug discovery; Pre-clinical research; Tumor microenvironment