Tumoroid-On-a-Plate (ToP): Physiologically Relevant Cancer Model Generation and Therapeutic Screening.

Abstract

Employing three-dimensional (3D) in vitro models, including tumor organoids and spheroids, stands pivotal in enhancing cancer therapy. These models bridge the gap between two-dimensional (2D) cell cultures and complex in vivo environments and offer versatile tools for comprehensive studies into cancer progression, drug responses, and tailored therapies. This study introduces the Tumoroid-on-a-Plate (ToP) device, an innovative ope-surface microfluidic platform designed to create predictive 3D models of solid tumors. The ToP device combines tumor mass, stromal cells, and extracellular matrix (ECM) components, to closely replicate the microenvironment of glioblastoma (GBM) and pancreatic adenocarcinoma (PDAC). Using the advanced ToP model and testing various GBM ECM compositions such as collagen and Rreelin within the model, we can assess how specific elements affect GBM invasiveness. The ToP in vitro model also enables screening chemotherapeutics such as temozolomide and iron-chelators in a single and binary treatment setting on the complex ECM-embedded tumoroids to evaluate their toxicity on GBM and PDAC models viability and apoptosis. Furthermore, co-culturing PDAC tumoroids with human-derived fibroblasts reveals the pro-invasive influence of stromal elements on tumor growth and drug response. This research underscores the value of advanced 3D models like ToP in advancing the understanding of cancer complexity and therapy responses.