New tools for cancer drug discovery

Oeiras, 08.04.2016

Cancer drug discovery has been limited by high rates of failure in clinical trials, despite positive laboratory tests suggesting good drug activity. Several types of tumour cell models are used in research labs and by pharmaceutical companies for discovery and pre-clinical testing of new anti-cancer drugs. Nevertheless, these models still fail to reconstruct the complexity of human solid tumours and do not allow for long term monitoring of the tumour progression.

Researchers from Catarina Brito Lab have developed a new method to cultivate tumour spheroids and stromal cell, which better mimic disease progression in vitro. They have combined for the first time cell microencapsulation in microspheres of alginate (a biocompatible hydrogel that does not interfere with cell function) with bioreactor culture systems that mimic biological conditions. In this way they could mantain co-cultures of tumour cell spheroids and stromal cells, that are stable in the lab for long periods of time (from weeks to up to several months), providing a better tool for drug screening and target validation in pre-clinical oncology.

These results have been recently published in the Journal of Biotechnology and in Biomaterials, one of the top leading journals in biotechnology.

 “We have developed a new culture system in which several of the changes that take place in the environment of tumour cancer cells, the so called dynamics of tumour microenvironment, occur. Therefore, our system makes it possible to observe and study tumour progression using cell culture and constitutes a new tool to study tumour-stroma crosstalk in disease progression and drug resistance mechanisms. Moreover, its design facilitates the adaptation to industrial scales, and therefore can be a useful tool in cancer drug discovery”, refers Catarina Brito, head of the Advanced Cell Models Lab (Animal Cell Technology Unit).

This work has been carried out at ITQB NOVA and iBET within IMI-funded project PREDECT and in close collaboration with several academic partners (IPATIMUP-i3S and Instituto Gulbenkian de Ciência) and pharmaceutical companies (AstraZeneca, Boehringer Ingelheim and Abbvie belonging to the PREDECT consortium). The published papers, which are freely accessible to all,  provide methods that the pharmaceutical industry can use in their quest to discover new effective medicines.

• Estrada MF, Rebelo SP, Davies EJ, Pinto MT, Pereira H, Santo VE, Smalley MJ, Barry ST, Gualda EJ, Alves PM Anderson E, Brito C (2016) Modelling the tumour microenvironment on long-term microencapsulation 3D co-cultures recapitulates phenotypic features of disease progression, Biomaterials 78, 50-61.
  http://dx.doi.org/10.1016/j.biomaterials.2015.11.030
• Santo VE, Estrada MF, Rebelo SP, Abreu S, Silva IM, Pinto C, Veloso SC, Serra T, Boghaert E, Alves PM, Brito C (2016) “Adaptable stirred-tank culture strategies for large scale production of multicellular spheroid-based tumor cell models”, Journal of Biotechnology, epub ahead of print 2016 Jan 24.
  http://dx.doi.org/10.1016/j.jbiotec.2016.01.031