Metastasis affects ~30% of breast cancer patients, and is responsible for nearly all cancer-related deaths, but by the time metastases are detected, patients are not treated with curative intent. In these patients, tumor cells had clearly disseminated from the primary tumor prior to surgery but remained indolent for varying periods of time. Very little is known about processes by which indolent disseminated tumor cells convert to life-threatening disease. Hence, it is currently impossible to accurately predict which patients will experience disease relapse.
Our lab studies the early phases of metastatic disease when patients harbor indolent tumor cells in the periphery at the time of their primary diagnosis. We previously showed that certain triple-negative breast cancers systemically support the outgrowth of disseminated, otherwise indolent tumors by secreting cytokines that activate bone marrow hematopoietic cells to become pro-tumorigenic (McAllister, et al., Cell, 2008; Elkabets, et al., JCI, 2011; Castano, et al, Ca Disc, 2013). Using models of luminal breast cancer, we discovered that certain tumors promote metastatic outgrowth by supporting angiogenesis via platelet activation (Kuznetsov, et al., Ca Disc, 2012). We termed this action-at-a-distance “systemic instigation”.
Our research is focused on identifying systemic factors that contribute to tumor progression and finding ways to interdict their function. Our findings highlight the systemic environment as an important component of disease progression that can be exploited to more accurately identify patients who would benefit from the appropriate therapies before they relapse.