Three-dimensional tumor cell growth models in vivo drug resistance mechanisms

The success rates for investigational cancer drugs in clinical development are poor, reflecting the current limitations of preclinical models in recapitulating relevant (patho-)physiological mechanisms of drug resistance, including autophagy. Recently, three-dimensional (3D) growth cultures have been introduced for preclinical drug testing to improve the lack of correlation between monolayer cell cultures and human tumors. Besides 3D growth, it is also important to simulate shear stress, compound flux and removal of metabolites, e.g. via bioreactor systems, through which culture medium is constantly pumped at a…