In Regard to Chen et al: Could GBM Cell Growth Be Suppressed by Both Palmitoylation Inhibitor and Depalmitoylation Inhibitor?

We read with great interest a recent study published in the International Journal of Radiation Oncology • Biology • Physics by Chen et al 1 Fan X Sun S Yang H et al. SETD2 palmitoylation mediated by ZDHHC16 in epidermal growth factor receptor-mutated glioblastoma promotes ionizing radiation-induced DNA damage. Int J Radiat Oncol Biol Phys. 2022; 113: 648-660 Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar regarding how SEDT2 palmitoylation mediated by ZDHHC16 in EGFR-mutated glioblastoma (GBM) promotes ionizing radiation-induced DNA damage. Chen et al found that palmitoylation of SEDT2 protein mediated by ZDHHC16 is crucial for maintaining SEDT2 protein stability, which, in turn, regulates DNA damage response via H3K36 trimethylation. They also identified that PalmB, a depalmitoylation inhibitor, enhanced DNA damage response via promoting SETD2 palmitoylation in glioma cells. Treatment of PalmB also exhibited strong tumor growth suppression in xenografted mice. Therefore, they concluded that target depalmitoylation is promising for patients with glioma undergoing radiation therapy. 1 Fan X Sun S Yang H et al. SETD2 palmitoylation mediated by ZDHHC16 in epidermal growth factor receptor-mutated glioblastoma promotes ionizing radiation-induced DNA damage. Int J Radiat Oncol Biol Phys. 2022; 113: 648-660 Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar We really appreciate the interesting observations and their conclusion. Meanwhile, we would like to highlight an important question that they raise.