Three dimensional engineered models to study hypoxia biology in breast cancer

Breast cancer is the second leading cause of mortality among women worldwide. Despite the available therapeutic regimes, variable treatment response is reported among different breast cancer subtypes. Recently, the effects of the tumor microenvironment on tumor progression as well as treatment responses have been widely recognized. Hypoxia and hypoxia inducible factors in the tumor microenvironment have long been known as major players in tumor progression and survival. However, the majority of our understanding of hypoxia biology has been derived from two dimensional (2D) models. Although many hypoxia-targeted therapies have elicited promising results in vitro and in vivo, these results have not been successfully translated into clinical trials. These limitations of 2D models underscore the need to develop and integrate three dimensional (3D) models that recapitulate the complex tumor-stroma interactions in vivo. This review summarizes role of hypoxia in various hallmarks of cancer progression. We then compare traditional 2D experimental systems with novel 3D tissue-engineered models giving accounts of different bioengineering platforms available to develop 3D models and how these 3D models are being exploited to understand the role of hypoxia in breast cancer progression.