Targeting tumor cell motility as a strategy against invasion and metastasis

Advances in diagnosis and treatment have rendered most solid tumors largely curable if they are diagnosed and treated before dissemination. However, once they spread beyond the initial primary location, these cancers are usually highly morbid, if not fatal. Thus, current efforts focus on both limiting initial dissemination and preventing secondary spread. There are two modes of tumor dissemination – invasion and metastasis – each leading to unique therapeutic challenges and likely to be driven by distinct mechanisms. However, these two forms of dissemination utilize some common strategies to accomplish movement from the primary tumor, establishment in an ectopic site, and survival therein. The adaptive behaviors of motile cancer cells provide an opening for therapeutic approaches if we understand the molecular, cellular, and tissue biology that underlie them. Herein, we review the signaling cascades and organ reactions that lead to dissemination, as these are non-genetic in nature, focusing on cell migration as the key to tumor progression. In this context, the cellular phenotype will also be discussed because the modes of migration are dictated by quantitative and physical aspects of the cell motility machinery.National Institute of General Medical Sciences (U.S.)National Cancer Institute (U.S.