Kathleen M. McAndrews1, Krishnan K. Mahadevan1 and Raghu Kalluri1,2,3 1Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA 2Department of Bioengineering, Rice University, Houston, Texas 77251, USA 3Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA Correspondence: rkallurimdanderson.org; kmmcandrewsmdanderson.org

The tumor microenvironment (TME) is a complex ecosystem of both cellular and noncellular components that functions to impact the evolution of cancer. Various aspects of the TME have been targeted for the control of cancer; however, TME composition is dynamic, with the overall abundance of immune cells, endothelial cells (ECs), fibroblasts, and extracellular matrix (ECM) as well as subsets of TME components changing at different stages of progression and in response to therapy. To effectively treat cancer, an understanding of the functional role of the TME is needed. Genetically engineered mouse models have enabled comprehensive insight into the complex interactions within the TME ecosystem that regulate disease progression. Here, we review recent advances in mouse models that have been employed to understand how the TME regulates cancer initiation, progression, metastasis, and response to therapy.