Seeking such an agent among FDA-approved drugs, our group found that ivermectin, an anti-parasitic drug used worldwide since 1975 to treat close to 1 billion people primarily for river blindness and other parasitic infections, promotes ICD in breast cancer cells. Among our other findings was evidence that ivermectin modulates the P2X4/P2X7 purinergic pathway, suggesting that ivermectin may further harness tumors’ intrinsic high extracellular levels of ATP for anti-cancer activity.
These promising in vitro results prompted us to move forward to in vivo studies using a common animal model of TNBC. In this model, breast tumors are “cold,” indicating little or no infiltrating T cells. Ivermectin treatment led to robust T-cell infiltration turning cold tumors into hot tumors with cancer cells showing markers of ICD in vivo.