ARTICLE ABSTRACT
The recalcitrant nature of triple-negative breast cancer (TNBC) calls for novel treatments. Acetalax (oxyphenisatin acetate) and bisacodyl, which have been and are extensively used orally as laxatives, have recently been reported to exhibit selective antiproliferative activity when incubated with cancer cells and xenograft models. Here, we show that they are both preferentially active in TNBC cell lines, and that their activity patterns overlap across the 1,000 cell lines of the Sanger database but are unique and distinct from the standard chemotherapies. Multivariate transcriptomic analyses demonstrate that expression of the ion transporter TRPM4 and two other cell surface genes predict the activity of both drugs. In vivo testing shows that both Acetalax and bisacodyl induce complete regression of different TNBC patient-derived xenografts. Acetalax pharmacokinetics shows a 5.8-hour terminal half-life and drug penetration in TNBC tumors and brain.
Acetalax and bisacodyl represent a prospective novel drug mechanism-of-action type, affect mitochondrial function and affect tumor growth in vivo. Their activity may be predicted by TRPM4 but with more accuracy adding other genes in multivariate analysis for triple negative breast cancer (TNBC). Acetalax has a biphasic mean half-life of 5.8 hours.
