sm-164 has been researched along with Lung-Neoplasms* in 1 studies
1 other study(ies) available for sm-164 and Lung-Neoplasms
Article | Year |
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The IAP Antagonist SM-164 Eliminates Triple-Negative Breast Cancer Metastasis to Bone and Lung in Mice.
The most challenging issue for breast cancer (BC) patients is metastasis to other organs because current therapies do not prevent or eliminate metastatic BC. Here, we show that SM-164, a small molecule inhibitor, which degrades inhibitor of apoptosis proteins (IAPs), eliminated early-stage metastases and reduced progression of advanced BC metastasis from MDA-MB-231 BC cells in bones and lungs of nude mice. Mechanistically, SM-164-induced BC cell death is TNFα-dependent, with TNFα produced by IL-4-polarized macrophages triggering MDA-MB-231 cell apoptosis in combination 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 did not kill adriamycin-resistant BC cells, while adriamycin inhibited SM-164-resistant BC cell growth, similar to parental cells. We conclude that SM-164 is a promising therapeutic agent for early stage bone and lung metastasis from triple-negative breast cancer that should be given prior to conventional chemotherapy. Topics: Animals; Apoptosis; Bone Neoplasms; Bridged Bicyclo Compounds, Heterocyclic; Cell Line, Tumor; Doxorubicin; Female; Humans; Inhibitor of Apoptosis Proteins; Lung Neoplasms; Mice; Mice, Nude; RANK Ligand; Triazoles; Triple Negative Breast Neoplasms | 2020 |