The progressive trend of modeling and drug screening systems of breast cancer bone metastasis

Abstract Bone metastasis is considered as a considerable challenge for breast cancer patients. Various in vitro and in vivo models have been developed to examine this occurrence. In vitro models are employed to simulate the intricate tumor microenvironment, investigate the interplay between cells and their adjacent microenvironment, and evaluate the effectiveness of therapeutic interventions for tumors. The endeavor to replicate the latency period of bone metastasis in animal models has presented a challenge, primarily due to the necessity of primary tumor removal and the presence of multiple potential metastatic sites. The utilization of novel bone metastasis models, including three-dimensional (3D) models, has been proposed as a promising approach to overcome the constraints associated with conventional 2D and animal models. However, existing 3D models are limited by various factors, such as irregular cellular proliferation, autofluorescence, and changes in genetic and epigenetic expression. The imperative for the advancement of future applications of 3D models lies in their standardization and automation. The utilization of artificial intelligence exhibits the capability to predict cellular behavior through the examination of substrate materials' chemical composition, geometry, and mechanical performance. The implementation of these algorithms possesses the capability to predict the progression and proliferation of cancer. This paper reviewed the mechanisms of bone metastasis following primary breast cancer. Current models of breast cancer bone metastasis, along with their challenges, as well as the future perspectives of using these models for translational drug development, were discussed.