Chapter 20 - Three-dimensional tumor model and their implication in drug screening for tackling chemoresistance

Abstract

Despite of having the initial positive responses of chemotherapy, many cancer patients experience relapse with continued tumor growth and metastasis due to development of drug resistance. Chemoresistance is one of the main reasons for treatment failure in cancer patients. Understanding the molecular mechanism of drug resistance and rewiring of chemoresistant cells to undergo drug-induced apoptosis are viable approaches to overcome chemoresistance. The traditional two-dimensional (2D) monolayer culture system has limitations to study drug resistance, as it does not mimic the in vivo tumor microenvironment (TME). In contrast, three-dimensional (3D) culture is an ideal model to study chemoresistance as it accurately recapitulates in vivo TME, that is enrichment of stem cells, cell to cell or cell to extracellular matrix interaction, and tumor heterogeneity. Recently, tumor heterogeneity and microenvironment have drawn much attention for its impact on tumor development, drug resistance, and patient outcome. Therefore, it is possible to carry out cell-based assays like drug screening, and drug action using 3D culture model to explore agents those overcome chemoresistance. Henceforth, 3D culture model can be an appropriate platform to identify anticancer agents with potential of future clinical relevance.