Tumoroid model undergoes developmental reprogramming that drives chemotherapeutic resistance

The tumor microenvironment (TME) consists of a unique biochemical signature that plays a significant role in cell proliferation, invasion, and metastasis in solid tumors. The development of hypoxia is a common phenomenon within the TME, that shapes the metabolic and signaling landscape of solid tumors. The work presented here utilizes a novel three-dimensional tumour model known as tumoroids, which are small, 2mm-long units of collagen containing a cancer cell line. Hypoxia has previously been shown to develop naturally in the model due to condensation caused by rapid proliferation within days of fabrication. By embedding triple negative breast cancer cells in the model, this project aimed to determine how drug resistance could be linked to the development of hypoxia within tumoroids as they condensed. Through the use of confocal imaging, hypoxic changes were tracked and aligned with protein level changes detected through western blot. This foundational work demonstrated that gene expression is consistently altered throughout the course of tumoroid development, indicating that the model has promising applications for studying TME dynamics in future projects.