The cancer exodus hypothesis establishes that circulating tumor cell clusters (CTC clusters) maintain their multicellular structure throughout the metastatic process. It was previously thought that these clusters must dissociate into single cells during metastasis.[1] According to the hypothesis, CTC clusters intravasate (enter the bloodstream), travel through circulation as a cohesive unit, and extravasate (exit the bloodstream) at distant sites without disaggregating, significantly enhancing their metastatic potential. This concept is considered a key advancement in understanding of cancer biology and CTCs role in cancer metastasis.[2][3]
Traditionally, it was believed that CTC clusters needed to dissociate into individual cells during their journey through the bloodstream to seed secondary tumors. However, recent studies show that CTC clusters can travel through the bloodstream intact, enabling them to perform every step of metastasis while maintaining their group/cluster structure.[3][2][4]
The cancer exodus hypothesis asserts that CTC clusters have several distinct advantages that increase their metastatic potential:
The cancer exodus hypothesis offers important insights into how metastasis occurs and highlights the significance of CTC clusters in cancer progression. Detecting and analyzing CTC clusters through liquid biopsies could offer valuable information about the aggressiveness and metastatic potential of cancers.[10][11] This information is particularly useful for identifying patients who may benefit from more aggressive treatment strategies.[2][12]
The hypothesis was developed due to several key studies, which have demonstrated the ability of CTC clusters to:
These findings underscore the critical role of CTC clusters in driving the metastatic cascade and suggest that CTC clusters could serve as important biomarkers in cancer diagnosis, prognosis, and treatment planning.[5] Additionally, understanding the mechanisms that allow CTC clusters to retain their structure and survive in circulation opens new avenues for targeted cancer therapies designed to disrupt this process.[15]
As research into the cancer exodus hypothesis progresses, new therapeutic strategies could emerge to specifically target CTC clusters. Blocking their formation, disrupting their cohesion, or preventing their ability to survive in the bloodstream could offer new ways to prevent metastasis in aggressive cancers. Continued studies will be essential to further elucidate the biological pathways involved in CTC cluster-mediated metastasis and develop potential treatment interventions.[16][17]
