The Use of FN‐Silk Networks as Extracellular Matrix‐Mimicking Support for 3D In Vitro Breast Cancer Models Improved the Model's Reproducibility in Drug Sensitivity

ABSTRACT To identify effective drugs for breast cancer treatment, it is essential to establish physiologically relevant models. Traditional models based on 2D cultures or 3D scaffold‐free spheroids lack the crucial cell–extracellular matrix (ECM) interactions, known to significantly impact drug sensitivity. A newly developed 3D culture format using a network of the recombinant spider silk protein FN‐silk has demonstrated ECM‐like interactions and maintenance of subtype‐specific marker expression in breast cancer cells. In the current study, chemotherapy drug treatment experiments were conducted on the breast cancer cell lines MCF‐7, MDA‐MB‐231, and SK‐BR‐3 cultured in 2D, spheroids, and FN‐silk networks. The results suggest that FN‐silk networks hold promise as a base for an in vitro 3D model assessing the effects of chemotherapeutic agents. Comparing drug responses revealed that cells cultured in FN‐silk networks were generally less sensitive to the drugs tested—as compared to 2D cultures—suggesting that FN‐silk‐supported 3D culture could have higher clinical relevance. Moreover, the results showed improved reproducibility with FN‐silk networks compared to spheroids. This study concludes that FN‐silk networks have the potential to support the establishment of a valuable 3D tumor model for the development of personalized breast cancer treatments and thereby contribute to improved success rates in drug development.