Metastasis Prevention: Focus on Metastatic Circulating Tumor Cells

Metastasis is the main cause of cancer death. Metastatic foci are derived from tumor cells that detach from the primary tumor and then enter the circulation. Circulating tumor cells (CTCs) are generally associated with a high probability of distant metastasis and a negative prognosis. Most CTCs die in the bloodstream, and only a few cells form metastases. Such metastatic CTCs have a stem-like and hybrid epithelial-mesenchymal phenotype, can avoid immune surveillance, and show increased therapy resistance. Targeting metastatic CTCs and their progenitors in primary tumors and their descendants, particularly disseminated tumor cells, represents an attractive strategy for metastasis prevention. However, current therapeutic strategies mainly target the primary tumor and only indirectly affect metastasis-initiating cells. Here, we consider potential methods for preventing metastasis based on targeting molecular and cellular features of metastatic CTCs, including CTC clusters. Also, we emphasize current knowledge gaps in CTC biology that should be addressed to develop highly effective therapeutics and strategies for metastasis suppression.

Automated summary

Metastasis, the spread of tumor cells from the primary site to other parts of the body, is a major cause of cancer-related deaths. Circulating tumor cells (CTCs) with stem-like and hybrid epithelial-mesenchymal phenotypes can evade immune surveillance and exhibit increased therapy resistance, contributing to the negative prognosis associated with distant metastasis. Targeting the molecular and cellular characteristics of metastatic CTCs, including CTC clusters, may hold promise for preventing metastasis and improving therapeutic outcomes.