publdcatdons: c. peitzsch, m. cojoc, l. hein, i. kurth, k. mäbert, f. trautmann, b. klink, e. schröck, m.p. wirth, m. krause, e.a. stakhovsky, g.d. telegeev, v. novotny, m. toma, m. muders, g.b. baretton, f.m. frame, n.j. maitland, m. baumann, a. dubrovska: an epigenetic reprogramming strategy to resensitize radioresistant prostate cancer cells, in cancer research, 2016 (doi: 10.1158/0008-5472.can-15-2116) m. cojoc, c. peitzsch, i. kurth, f. trautmann, l.a. kunz- schughart, g.d. telegeev, e.a. stakhovsky, j.r. walker, k. simin, s. lyle, s. fuessel, k. erdmann, m.p. wirth, m. krause, m. baumann, a. dubrovska: aldehyde dehydrogenase is regulated by β-catenin/tcf and promotes radioresistance in prostate cancer progenitor cells, cancer research, 2015 (doi: 10.1158/0008-5472.can-14-1924) 20 title sensitization for the diseased cells via changes in the methyl groups, environmental conditions can directly influence whether genes can be transcribed or not, "because methylation affects how tightly or loosely the dna is packed in the chromosome," says peitzsch. in 2016, the team demonstrated dna methylation can be changed by the x-rays: a chromosome opens up and some genes can be transcribed, investing the cells with properties like the ability to form tumors, to repair dna damage more efficiently or to migrate from their initial side. dubrovska, peitzsch and their colleagues identified one of the genes that are transcribed: aldh1a1, encodes the enzyme aldehyde dehydrogenase. it helps the cells to become more radioresistant by protecting against oxidative stress and dna damage. this gave the researchers a foothold for interrupting the transformation of the tumor cell into a radioresistant cancer stem cell. when they prevented the transcription of this gene with a certain chemical drug, which affects histone methylation, the cells once again responded more sensitively to x-rays. the radiation damage to the dna was greater and more tumor cells died. "our results indicate that certain drugs, which can prevent changes in histone methylation after ionizing radiation, will potentially be able to increase the effectiveness of radiotherapy in future," explains anna dubrovska. as promising as this initial evidence may be, the team still has a great deal of work ahead of it. claudia peitzsch is currently investigating other substances to find candidates that might potentially enhance the radiosensitivity of cancer stem cells in prostate carcinomas. one doctoral student is studying the same phenomenon in other types of cancer: "and it looks like different tumor types have a different potential for radiation- induced epigenetic reprogramming," says anna dubrovska. this fact makes the undertaking more difficult but that again is typical for science and completely in line with its mantra: new knowledge always generates new challenges, too. contact _institute of radiooncology – oncoray at hzdr prof. anna dubrosvka a.dubrovska@hzdr.de _national center for radiation research in oncology – oncoray / national center for tumor diseases – nct dresden dr. claudia peitzsch claudia.peitzsch@oncoray.de _institute of radiation physics at hzdr dr. benjamin lutz b.lutz@hzdr.de