Progression to Metastasis of Solid Cancer

Abstract

Metastatic dissemination of cancer cells, their colonization at distal sites, and ultimate disruption of tissue physiology are the root causes of most deaths from solid cancers, particularly in tumor types where the primary lesion can be easily dissected and discarded [...].

Figure 1

Unique hallmarks of the metastatic cascade. Primary tumors are highly heterogeneous due to clonal evolution and local competition. Dominant subclones with mutations (A-B-C or A-B-D) may not necessarily sprout metastases. In the depicted scenario, a smaller clone, A-E, has acquired an additional mutation, designated m (A-E-m) at the primary site or post-dissemination that promotes metastatic disease or drug-resistance. Steps in the metastatic cascade and unique hallmarks that may be therapeutically targeted are indicated. A major theme is the plasticity of disseminating tumor cells that enables progression through the “long and winding road” of the metastatic cascade (see text for details).