3D Cell Models in Radiobiology: Improving the Predictive Value of In Vitro Research

Cancer is intrinsically complex, comprising both heterogeneous cellular composition and extracellular matrix. In vitro cancer research models have been widely used in the past to model and study cancer. Although two-dimensional (2D) cell culture models have traditionally been used for cancer research, they have many limitations, such as the disturbance of interactions between cellular and extracellular environments and changes in cell morphology, polarity, division mechanism, differentiation and cell motion. Moreover, 2D cell models are usually monotypic. This implies that 2D tumor models are ineffective at accurately recapitulating complex aspects of tumor cell growth, as well as their radiation responses. Over the past decade there has been significant uptake of three-dimensional (3D) in vitro models by cancer researchers, highlighting a complementary model for studies of radiation effects on tumors, especially in conjunction with chemotherapy. The introduction of 3D cell culture approaches aims to model in vivo tissue interactions with radiation by positioning itself halfway between 2D cell and animal models, and thus opening up new possibilities in the study of radiation response mechanisms of healthy and tumor tissues.