Repurposing NFκB and HDAC inhibitors to individually target cancer stem cells and non-cancer stem cells from mucoepidermoid carcinomas

Drug resistance remains a major obstacle in the treatment of mucoepidermoid carcinomas (MEC) lead-ing to tumor recurrence, disease progression, and metastasis. Emerging evidence suggests that drug resistance is mediated by the presence of a highly adaptative subpopulation of cancer cells known as cancer stem cells (CSC). We have previously reported that solid tumors use NFkB signaling as a chemotherapy-resistant mechanism. We have also shown that interfering with the epigenome of solid tumors is an effective strategy to control the popula-tion of CSC. Here, we sought to investigate the effects of the NFkB inhibitor emetine and the HDAC inhibitor SAHA on the biology of MEC CSC and assessed whether this combination therapy would favor the standard of care therapy comprised of the administration of Cisplatin (CDDP). Our findings suggested that the administration of low concen-trations of emetine and SAHA is more effective in disrupting CSC in MEC, while the administration of emetine in combination with CDDP constitutes an effective therapy to target non-CSC MEC tumor cells.

Automated summary

Drug resistance is a major hurdle in the treatment of mucoepidermoid carcinomas (MEC), mainly due to the presence of cancer stem cells (CSC). In this study, the effects of NFkB inhibitor emetine and HDAC inhibitor SAHA on MEC CSC were investigated. The findings suggest that low concentrations of emetine and SAHA are more effective in disrupting CSC, while emetine in combination with CDDP is an effective therapy for non-CSC MEC tumor cells.