The metastatic cycle: metastatic niches and cancer cell dissemination

The concept of a unidirectional cascade of metastatic events has been replaced in recent years by the metastatic cycle -the concept of a dynamic feed forward cycle of metastatic niches that evolve upon reciprocal interactions with the primary tumor and disseminating cancer cells. Primary tumors interact with pre-metastatic sites preparing organ-specific pre-metastatic niches. Metastasis-initiating cells home to and succumb to interactions with developing organ-specific metastatic niches, and secondary recirculating cancer cells interact back with the primary. Metastatic tropism as well as metastatic disease progression are a result of this feed forward cycle of dynamic, reciprocal interactions of cancer cells with their diverse metastatic niches. A better understanding of the multifaceted contributions of the organ-specific metastatic niches and their complex changes on cancer cell dissemination and of the mutual effects of the cellular and molecular mechanisms involved will open new avenues to better therapies for hitherto intractable progressive disease states of cancer patients and for adjuvant treatment options preventing relapses in tumor-free patients.