Epigenetic plasticity as a novel target for cancer treatment

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Glioblastoma is the most common and deadly primary brain tumor, which is characterized by intratumoral and intertumoral heterogeneity with histologically different types of cells. Such multiple distinct subpopulations of cancer cells within tumors link to the existence of cells that survive surgery and chemotherapy to form recurrent lesions that are resistant to further treatments. Elucidating the molecular mechanisms underlying tissue heterogeneity of glioblastoma is a fundamental requirement for the development of effective treatments for this dreadful disease. We revealed that H3K27me3 mediated by EZH2/PRC2, which controls tumor cell plasticity, may provide a target to restrict the functional heterogeneity in tumors, a core challenge to all cancer cell-centric drugs given the huge reservoir of resistance mechanisms which such heterogeneity confers. In order to identify the EZH2/PRC2 inhibitor, we developed a high-throughput screening for chemicals and assayed 15,000 compounds.