Mathematical modeling of tumor-tumor distant interactions supports a systemic control of tumor growth

Interactions between different tumors within the same organism have major clinical implications, especially in the context of surgery and metastatic disease. Three main explanatory theories (competition, angiogenesis inhibition and proliferation inhibition) have been proposed but precise determinants of the phenomenon remain poorly understood. Here we formalized these theories into mathematical models and performed biological experiments to test them with empirical data. In syngeneic mice bearing two simultaneously implanted tumors, growth of only one of the tumors was significantly suppressed (61% size reduction at day 15, pMajor findings In mice bearing two tumors implanted simultaneously, tumor growth was suppressed in one of the two tumors. Three theories of this phenomenon were advanced and assessed against the data. As formalized, a model of competition for nutrients was not able to explain the growth behavior as well as indirect, angiogenesis-regulated inhibition or a third model based on direct systemic inhibition. This last model offers a depiction of concomitant resistance that provides an improved theoretical basis for tumor growth control and may also find utility in therapeutic planning to avoid post-surgery metastatic acceleration.

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