Identification of non-oncology drugs with activity against inflammatory and triple-negative breast cancer cell lines

Inflammatory breast cancer (IBC) and triple-negative breast cancer (TNBC) are subtypes of breast cancer with the lowest 5-year survival rates. One potential approach to increase survival rates for these cancers may be to identify tolerable and inexpensive daily maintenance therapies that could be administered in between standard of care treatments. The present study aimed to identify non-oncology drugs (NODs) that show activity against IBC/TNBC that could be repurposed for this use. Thus, a collection of NODs were screened and curated from a published database using cell line SUM-149, which is both an IBC and TNBC cell line (TN-IBC). In a parallel screening approach, a subset of these NODs were tested for activity against two other TNBC cell lines. Together, 15 drugs with activity against this IBC cell line were identified and grown as spheroids. A number of these drugs have not been previously identified as having activity in an IBC cell line. In addition, eight of these were understudied for TNBC and, therefore, they were tested against three TNBC cell lines grown as spheroids, resulting in variable breadth of activities. Drug potency (GI₅₀) was also assessed relative to their C_max reported in human studies. Eltrombopag, a thrombocytopenia drug, was active against SUM-149 and two other TNBC cell lines with a GI₅₀:C_max ratio of ~1. Papaverine, a vasodilator, was also active against SUM-149 and one other TNBC cell line with a GI₅₀:C_max ratio of ~2. Mozavaptan, a hyponatremia drug, inhibited proliferation in 4 out of 5 cell lines (all except SUM-149) with GI₅₀=2.7-7.6 µM (C_max unknown). Spironolactone (GI₅₀:C_max=10) had anti-proliferative activity only against SUM-149, suggesting a unique vulnerability. Overall, our data indicated that eltrombopag, papaverine and other identified NODs may have potential for being repurposed for TN-IBC and TNBC in general.