Tissue-engineered Cancer Models in Drug Screening

Abstract

Novel anticancer therapeutics are urgently required to meet the increasing global cancer burden associated with aging populations. The development of new drugs is hindered by high failure rates at clinical stages, which are partly attributable to inadequate screening strategies which rely heavily on the use of cancer cell lines cultured in 2D and animal models. Although each of these models has certain advantages, they generally fail to accurately represent the human pathophysiology of malignant tumors. Emerging tissue-engineered 3D cancer models designed to better mimic in vivo tumors have the potential to provide additional tools to complement those currently available to address this limitation and improve drug discovery and translation in the long run. To successfully develop and implement a 3D cancer model for drug screening, several key steps are necessary: selection of the tumor type and concept to be modeled, identification of the essential components and set up of the model, model validation, establishment of a scalable manufacturing and analysis pipeline, and selection of a drug library to perform the screen. In this chapter, we elaborate on and evaluate each of these decision steps, highlight the challenges associated with each step, and discuss opportunities for future research.