“…This model is more closely related to original tumors with respect to cell morphology, metabolic and proliferative gradients, oxygen and drug penetration, cell-cell junctions, kinases activation and other parameters, compared to the cancer cell monolayers (Friedrich et al, 2009). Spheroid cells have an enhanced resistance to many of the commonly used anticancer drugs (Dessoize et al, 2000;Yoshida et al, 2008), showing dramatically lower cytotoxicity against 3D cancer spheroids compared to monolayer cultures, and exhibit chemoresistance which recapitulates this resistant phenotype in vivo (Dubessy et al, 2000;Durand et al, 2001;Friedrich et al, 2009). Increased resistance of spheroid cells to ionizing radiation was first demonstrated by Sutherland and colleagues (Inch et al, 1970;Sutherland et al, 1971).…”