Preclinical microscopy has greatly enhanced our mechanistic understanding of cancer invasion and metastasis, the contribution of the tumour microenvironment to metastatic progression, and how invasion and the microenvironment jointly support cancer cell survival and resistance. Using organotypic models in vitro, live-cell imaging in three-dimensional (3D) tissue culture has identified how cytoskeletal, adhesion and protease systems drive invasion and metastasis [1]. When altered at the molecular level, these pathways underlie the unexpected diversity of the invasive process [2]. The recent use of intravital microscopy has further suggested that cancer invasion into interstitial stroma in vivo: (1) occurs mostly as collective invasion in which cells remain coupled to neighbouring cancer cells, (2) is guided by and responsive to signals delivered by connective tissue structures and (3) that invasion pathways cross-talk with pathways of cancer cell survival and resistance to anticancer therapy [3].