The emerging molecular machinery and therapeutic targets of metastasis

•We highlight the challenges in making translational advances in metastasis research.•We delineate the role of epithelial–mesenchymal plasticity and CSCs.•We review emerging molecular determinants and therapeutic targets of metastasis.•We discuss the link between metastasis and therapy resistance.

Metastasis is a 100-year-old research topic. Technological advances during the past few decades have led to significant progress in our understanding of metastatic disease. However, metastasis remains the leading cause of cancer-related mortalities. The lack of appropriate clinical trials for metastasis preventive drugs and incomplete understanding of the molecular machinery are major obstacles in metastasis prevention and treatment. Numerous processes, factors, and signaling pathways are involved in regulating metastasis. Here we discuss recent progress in metastasis research, including epithelial–mesenchymal plasticity, cancer stem cells, emerging molecular determinants and therapeutic targets, and the link between metastasis and therapy resistance.