Evaluation of the response to neoadjuvant chemotherapy of breast cancer cells cultured in 3D bioprinted models
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- Breast cancer remains a major health concern, and response to neoadjuvant chemotherapy (NAC) can vary considerably between patients. This variability is partly influenced by the tumour microenvironment, which is only partially reproduced by conventional 2D culture models. In this context, 3D bioprinted models offer a promising approach to better mimic cell–matrix interactions and investigate treatment response in a more relevant environment. This Master’s thesis aimed to evaluate the response of two breast cancer cell lines, MCF-7 and ZR-75.1, to NAC in two distinct 3D bioprinted hydrogels, A1G7 and HAMA1/GelMA7, which differ in their composition, crosslinking method and mechanical properties. Cells were cultured for 14 days and exposed to a paclitaxel–epirubicin combination from D7. Treatment response was assessed using CellTiter-Glo® to measure the adenosine triphosphate (ATP)-dependent signal and reverse transcription quantitative PCR (RT-qPCR) to analyse the expression levels of selected genes. Under non-treated (NT) conditions, both hydrogels supported cell maintenance and expansion over time, although the increase in the ATP-dependent signal was overall greater in A1G7 than in HAMA1/GelMA7, suggesting an influence of the 3D microenvironment on cell behaviour. NAC induced a marked decrease in the ATP-dependent signal in all four cell line–hydrogel combinations, with a stronger effect observed at D14. A trend towards a higher residual signal in HAMA1/GelMA7 was observed at D10, suggesting an apparently lower sensitivity to treatment in this matrix, although this trend was not consistently maintained at D14. The transcriptional analysis was limited by variability in ribonucleic acid (RNA) extract quality, preventing a reliable assessment of the effect of NAC on gene expression. Nevertheless, some exploratory trends were observed under NT conditions and will require further validation. Overall, these results show that both 3D bioprinted models can support breast cancer cell culture and reveal a response to NAC. They also suggest that the 3D microenvironment may influence cellular behaviour and treatment response, supporting further optimisation of these models to investigate mechanisms involved in chemoresistance.