State of the art modelling of the breast cancer metastatic microenvironment: where are we?

Abstract

Metastatic spread of tumour cells to tissues and organs around the body is the most frequent cause of death from breast cancer. This has been modelled mainly using mouse models such as syngeneic mammary cancer or human in mouse xenograft models. These have limitations for modelling human disease progression and cannot easily be used for investigation of drug resistance and novel therapy screening. To complement these approaches, advances are being made in ex vivo and 3D in vitro models, which are becoming progressively better at reliably replicating the tumour microenvironment and will in the future facilitate drug development and screening. These approaches include microfluidics, organ-on-a-chip and use of advanced biomaterials. The relevant tissues to be modelled include those that are frequent and clinically important sites of metastasis such as bone, lung, brain, liver for invasive ductal carcinomas and a distinct set of common metastatic sites for lobular breast cancer. These sites all have challenges to model due to their unique cellular compositions, structure and complexity. The models, particularly in vivo, provide key information on the intricate interactions between cancer cells and the native tissue, and will guide us in producing specific therapies that are helpful in different context of metastasis.