Cell: new breakthrough in drug resistance of tumor! This new therapy is specially designed to kill drug-resistant melanoma cells!

May 18, 2018 / BIOON /-- highlights of this study: 1) ROS level of BRAF inhibitor resistant melanoma increases; histone deacetylase inhibitor increases ROS level by inhibiting SLC7A11; resistance of BRAF inhibitor causes susceptibility to histone deacetylase inhibitor; in patients, histone deacetylase inhibitor selectively kills resistant cells Photo source: cell's resistance to BRAF (V600E) mutant melanoma treated with BRAF and MEK kinase inhibitors is always due to the reactivation of mitogen activated protein kinase (MAPK) pathway In order to find new therapies for these patients, researchers from the Dutch Institute of oncology and other institutions, under the leadership of Professor Rene Bernards, tried to find out the defects acquired by MAPK inhibitor resistant melanoma patients The researchers found that tolerance to BRAF + MEK inhibitors was associated with increased ROS levels The researchers then used the histone deacetylase inhibitor vorinolta to inhibit SLC7A11, resulting in the rise of ROS levels in resistant cells to lethal levels, which led to apoptosis only in resistant cells Using vorinolta to treat mice with BRAF inhibitor resistant melanoma can make the tumor subside significantly At the same time, in a study of patients with malignant BRAF + MEK inhibitor resistant melanoma, the researchers found that vorinolta can selectively remove drug-resistant tumor cells, which also provides clinical evidence for the new therapy Reference: Wang et.al., an acquired vulnerability of drug resistant melanoma with therapeutic potential, cell, May 10, 2018, DOI: 10.1016/j.cell.2018.04.012