Advancing cancer therapeutics: Integrating scalable 3D cancer models, extracellular vesicles, and omics for enhanced therapy efficacy.

Cancer remains as one of the highest challenges to human health. However, anticancer drugs exhibit one of the highest attrition rates compared to other therapeutic interventions. In part, this can be attributed to a prevalent use of in vitro models with limited recapitulative potential of the in vivo settings. Three dimensional (3D) models, such as tumor spheroids and organoids, offer many research opportunities to address the urgent need in developing models capable to more accurately mimic cancer biology and drug resistance profiles. However, their wide adoption in high-throughput pre-clinical studies is dependent on scalable manufacturing to support large-scale therapeutic drug screenings and multi-omic approaches for their comprehensive cellular and molecular characterization. Extracellular vesicles (EVs), which have been emerging as promising drug delivery systems (DDS), stand to significantly benefit from such screenings conducted in realistic cancer models. Furthermore, the integration of these nanomedicines with 3D cancer models and omics profiling holds the potential to deepen our understanding of EV-mediated anticancer effects. In this chapter, we provide an overview of the existing 3D models used in cancer research, namely spheroids and organoids, the innovations in their scalable production and discuss how omics can facilitate the implementation of these models at different stages of drug testing. We also explore how EVs can advance drug delivery in cancer therapies and how the synergy between 3D cancer models and omics approaches can benefit in this process.