Improved tumor cell models are paramount to overcome current shortcomings of pre-clinical research and drug discovery

The team from the Advanced Cell Models Laboratory in the Animal Cell Technology Unit, based at Instituto de Biologia Experimental e Tecnológica (IBET) and Instituto de Tecnologia Química e Biológica António Xavier (ITQB) has been invested on the development of novel advanced tumor cell models with the ability to recapitulate certain features of tumor microenvironment, namely their heterogeneity and complex cellular composition. It has been demonstrated by several authors that tumor microenvironment plays a major role on tumor progression and drug response. Therefore, the incorporation of these features on the design of novel tumor cell models is essential to improve the predictive value of drug efficacy of these models.

If on one hand the implementation of more advanced tumor cell models to recapitulate certain tumor stages or events seems rather logic, on the other hand this will only be truly relevant and translational if these models are amenable for industrial platforms and high-throughput systems.

The team led by Dr. Catarina Brito has been collaborating with several industrial partners towards the implementation of these advanced cell models in industrial settings. This has been the particular focus of Dr. Vítor Espírito Santo, in combined efforts with the pharmaceutical company AbbVie based in Chicago (USA).

The impact of this strategy in pre-clinical research and in the reduction of drug attrition rates in clinical trials is expected to be significant. This work describes the more recent developments, the key factors to have in account and new directions in this field of research.

Authors and Affiliations:

Vítor E. Santo^1,2, Sofia P. Rebelo^1,2, Marta F. Estrada^1,2, Paula M. Alves^1,2, Erwin Boghaert³, Catarina Brito^1,2

¹ iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, Portugal.

² Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal.

³ AbbVie, 1 North Waukegan Road, North Chicago, IL 60064-6098, USA.

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.

Journal: Biotechnology Journal

Link: http://onlinelibrary.wiley.com/doi/10.1002/biot.201600505/full