Cell-intrinsic and microenvironmental determinants of metastatic colonization

Abstract

Cancer metastasis is a biologically complex process that remains a major challenge in the oncology clinic, accounting for nearly all of the mortality associated with malignant neoplasms. To establish metastatic growths, carcinoma cells must disseminate from the primary tumour, survive in unfamiliar tissue microenvironments, re-activate programs of proliferation, and escape innate and adaptive immunosurveillance. The entire process is extremely inefficient and can occur over protracted timescales, yielding only a vanishingly small number of carcinoma cells that are able to complete all of the required steps. Here we review both the cancer-cell-intrinsic mechanisms and microenvironmental interactions that enable metastatic colonization. In particular, we highlight recent work on the behaviour of already-disseminated tumour cells, since meaningful progress in treating metastatic disease will clearly require a better understanding of the cells that spawn metastases, which generally have disseminated by the time of initial diagnosis. Metastatic colonization involves cancer-cell-intrinsic mechanisms and microenvironmental interactions, and a better understanding of the factors that influence the final, post-extravasation phases is crucial for therapeutically targeting metatstasis.