The IAP Antagonist SM-164 Eliminates Triple-Negative Breast Cancer Metastasis to Bone and Lung in Mice

Probably the most challenging problem for cancer of the breast (BC) patients is metastasis with other organs because current therapies don’t prevent or eliminate metastatic BC. Here, we reveal that SM-164, a little molecule inhibitor, which degrades inhibitor of apoptosis proteins (IAPs), eliminated early-stage metastases and reduced advancement of advanced BC metastasis from MDA-MB-231 BC cells in bones and lung area of nude rodents. Mechanistically, SM-164-caused BC cell dying is TNFa-dependent, with TNFa created by IL-4-polarized macrophages triggering MDA-MB-231 cell apoptosis in conjunction with SM-164. SM-164 also inhibited expression of RANKL, which mediates interactions between metastatic BC and host microenvironment cells and induces osteoclast-mediated osteolysis. SM-164 didn’t kill adriamycin-resistant BC cells, while SM-164 adriamycin inhibited SM-164-resistant BC cell growth, much like parental cells. We conclude that SM-164 is really a promising therapeutic agent for initial phase bone and lung metastasis from triple-negative cancer of the breast that needs to be given just before conventional chemotherapy.