Kinetics of cancer metastasis

Abstract

The formation of metastases during cancer is now considered to be induced by migrating metastatic stem cells (MetSCs) in preexisting niches or niches induced by MetSCs or tumor-derived exosomes (TDEs). I propose and compare two simplest generic models describing these two scenarios. The number of tumors is predicted (i) to increase exponentially in the case of preexisting niches and (ii) to diverge during a finite time interval in the case of induced niches. The latter prediction is novel and of interest because rapid collapse in the end of a finite time interval is a well-known feature of the cancer metastasis. Two advanced models describing the two scenarios of cancer metastasis have been scrutinized as well. These models clarify the likely role of various specific factors in the metastasis. In particular, the equations derived in the framework of the advanced model with preexisting niches have been solved analytically allowing (i) to clarify the factors determining the duration of the period from the initiation of the primary tumor to the phase when the metastases start to dominate, (ii) to estimate the number of metastases in the end of this period, and (iii) to explains why the use of chemotherapy typically results in the improvement of the patient state only for a relatively short period. The equations derived in the framework of the advanced model with induced niches have no analytical solution, and their analysis merits additional attention.