Pharmaceutical companies lose every year billions dollars to test the toxicity and efficacy of the new drug(s). The drug development process may last around 7-10 years.1 Only 5% of the process can lead to the approval of a new drug.2 The main reason for this negative trend is the lack of accuracy of the screening model(s) (in vitro and in vivo) adopted in the preclinical trials. Thus, there is an urgent need to develop faster and more efficient screening platforms, which may overcome the limit of using flat cell cultures and animals in the first stage of the drug development process.3,4 The development of a novel 3D tumor culture system is bridging the gap between in vitro and in vivo methods for drug screening in order to recapitulate the complexity of the human tissue microenvironment and attain more reliable drug response. In this work, a heterotypic breast cancer model is realized by seeding breast cancer cells and normal fibroblasts on to silk protein fibroin freeze-dried scaffolds. The 3D breast cancer model is being employed as a testing platform to evaluate the efficacy of doxorubicin, which is a chemotherapeutic agent used to treat the breast cancer. The 3D homotypic cultures are used as control to evaluate the drug response in this 3D model. This model enlightens the mechanism of tumor and extracellular matrix remodeling. The model is also a straightforward 3D platform for drug testing due to its easy-to-use and cost-effective features. This 3D breast cancer model may also be useful for better understanding of the mechanisms behind chemo-resistance and metastatic spread.
This work is supported by the European Union Framework Programme for Research and Innovation Horizon 2020 under grant agreement nº 668983 — FoReCaST, FROnTHERA and the FCT project BREAST-IT (IF/028168/2017)
1. Edington, C. D. et al. Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies. Sci. Rep. 1–18 (2018). doi:10.1038/s41598-018-22749-0
2. Rodenhizer, D., Dean, T., D’Arcangelo, E. & McGuigan, A. P. The Current Landscape of 3D In Vitro Tumor Models: What Cancer Hallmarks Are Accessible for Drug Discovery? Adv. Healthc. Mater. 1701174, 1701174 (2018).
3. Caballero, D. et al. Organ-on-chip models of cancer metastasis for future personalized medicine: From chip to the patient. Biomaterials 149, 98–115 (2017).
4. Rodrigues, T. et al. Emerging tumor spheroids technologies for 3D in vitro cancer modeling. Pharmacol. Ther. 184, 201–211 (2018).