Meet me halfway: Are in vitro 3D cancer models on the way to replace in vivo models for nanomedicine development?

The hallmarks of three-dimensional (3D) cancer model. The complexity of elements and their roles in tumor progression can be recapitulated in vitro in 3D models of cancer. The creation of 3D tumor cell cultures opens the possibility to study: (a) extracellular matrix (ECM) composition and the rheological properties of tumor tissues; (b) tumor cells and their microenvironment cellular functions and interactions, in (c) a vascularized- and size- controlled 3D-bioprinted tissue; (d) drug toxicity and efficacy of nanomedicines, including immunotherapies, which can be exploited for prediction of drug combinations. Created with BioRender.com [Display omitted] • 3D models may bridge the translational gap between 2D cultures and animal studies. • 3D cancer models may alter the currently accepted ideal properties of nanomedicines. • 3D models can predict nanomedicine efficacy facilitating personalized cancer therapy. The complexity and diversity of the biochemical processes that occur during tumorigenesis and metastasis are frequently over-simplified in the traditional in vitro cell cultures. Two-dimensional cultures limit researchers' experimental observations and frequently give rise to misleading and contradictory results. Therefore, in order to overcome the limitations of in vitro studies and bridge the translational gap to in vivo applications, 3D models of cancer were developed in the last decades. The three dimensions of the tumor, including its cellular and extracellular microenvironment, are recreated by combining co-cultures of cancer and stromal cells in 3D hydrogel-based growth factors-inclusive scaffolds. More complex 3D cultures, containing functional blood vasculature, can integrate in the system external stimuli (e.g. oxygen and nutrient deprivation, cytokines, growth factors) along with drugs, or other therapeutic compounds. In this scenario, cell signaling pathways, metastatic cascade steps, cell differentiation and self-renewal, tumor-microenvironment interactions, and precision and personalized medicine, are among the wide range of biological applications that can be studied. Here, we discuss a broad variety of strategies exploited by scientists to create in vitro 3D cancer models that resemble as much as possible the biology and patho-physiology of in vivo tumors and predict faithfully the treatment outcome. [ABSTRACT FROM AUTHOR]