Drug Screening and Contrasting Sensitivities: Adenoid Cystic Carcinoma Cancer Stem Cells and Tumor Cells Differentially React to Histone Modifier Drugs

Abstract

Abstract Background adenoid cystic carcinoma (ACC), a rare malignancy often treated through a multidisciplinary approach, is noted for its slow progression and aggressive behavior. This study focuses on the impact of histone modification drugs (HMD) on ACC tumors and the implications for treatment. Methods: by analyzing the effects of HMD on Cancer Stem Cells (CSC) and non-CSC tumor cells, we investigated the inhibitory effect of various histone-modifying compounds on ACC tumor cells. Our dual-pronged approach used reductions in sphere size and increased cell death as indicators of drug efficacy, employing diverse compounds targeting histones. Results: subsequent validation revealed promising results, with specific drugs showing significant cytotoxicity. Moreover, several as-yet untried in ACC clinical trials showed potential, notably UNC0638, a histone methyltransferase inhibitor, and ITF2357 (Givinostat), an HDAC inhibitor that exhibited significantly high cell-death percentages. Also examined was the specific application of distinct HMD to non-cancer stem cells within ACC tumors. Conclusions: the findings underline the importance of identifying drugs capable of targeting CSC independently from non-CSC tumor cells, as both populations of cells present contrasting sensitivities.