From 2D to 3D: Advancing preclinical platforms in cancer models. Chehade H et al. AACR2025

Two-dimensional (2D) cell cultures have been extensively used as tools to predict preclinical outcomes before proceeding to expensive animal studies despite their limited success in replicating in vivo studies. To better mimic the physiological conditions of a tumor, a three-dimensional (3D) platform was developed utilizing different human and mouse cancer cell lines. Comparing the morphology (microscopic imaging) and cytotoxicity (IC50) of 3D cultures to 2D cultures and to in vivo revealed morphological and cytotoxicity differences between 2D and 3D with the 3D having better correspondence to in vivo studies compared to 2D. These findings underscore the efficiency and predictability of this 3D platform, and highlighting its potential to better predict treatment responses and to help identify drug resistance mechanisms.