LAUSR

Disease researchers have well studied the molecular and cellular properties of cell models propagated in two-dimensional (2D) culture. However, a lack of advanced in vitro and in vivo models has significantly impeded breakthroughs in understanding the fundamental mechanisms involved in diseases and thus, the development of new therapeutic strategies for patients. To change this situation, it has been deemed worthwhile to develop more physiologically relevant research models for mechanism-based target identification and drug discovery. Recently, new technologies and the refinement of existing technologies in preclinicalmodels have emerged. In particular, three-dimensional (3D) cell culture systems, which are used to model spheroids, organoids, and tissue heterogeneity, show promise, as they are more realistic and able to recapitulate the biological and physiological properties and functions of cultured cells and tissues. These new platforms, together with fit-forpurpose animal models, are key to success in bridging the gap between research and clinic. Given this methodological advancement, we examine new opportunities for the development and application of medical research models in a range diseases and therapeutics and disseminate the latest findings in basic and translational research. In the present Research Topic, we have garnered several contributors to demystify novel 3D and animalmodels systems, explore the developments and challenges, and provide evidence-informed insights for facilitating enablers of knowledge translation. Recently, the zebrafish (Danio rerio) have proven to be promising for the tumor microenvironment (TME) modeling. Teng’s team has performed pioneer studies using costeffective zebrafish-cancer models (Teng et al., 2013; Shao et al., 2013; Xie et al., 2015; Xie et al., 2016; Shull et al., 2017). Combining different lines of discoveries in this cutting-edge field, this team systemically reviewed the recent ways zebrafish models have contributed to our understanding of cancer cell plasticity and tumor heterogeneity that modulated by TME (Loveless et al.). They also attempted to highlight how zebrafish models lend their utility to provide new insights into the various cellular and molecular mechanisms driving TME dynamics and tumor support. While zebrafish possess attractive advantages to assess tumor microenvironment interactions within the context of the immune system and later within the metastatic cascade, exploration into its capacity as tool to investigate TME interactions and drive patient therapies forward has only just begun. There is no doubt that the mouse is the foremost mammalian model for studying human diseases and human health. In particular, genetically engineered mouse models have significantly contributed to our understanding of cancer biology and treatment response. It has also been well accepted that hormone-sensitive diseases are highly associated with age; thus, understanding how aging influences disease risk is quite important. To seek the answer, Liu and his group members established a novel virus-assisted spatially and temporally controlled Pten-null (referred to as Pten) mouse model at different ages of adult mice (Liu et al.). This study provides a novel experimental model for Edited and reviewed by: Paula Soares, Universidade do Porto, Portugal