Nat Med: inhibition of G9a / DNMT network is expected to treat muscle invasive bladder cancer

July 7, 2019 / Biovalley BIOON / - -- bladder cancer is fatal in its advanced stage of muscle infiltration, and the treatment progress in this area is very limited Recent molecular characterization has identified new genetic / epigenetic drivers and potential therapeutic targets for bladder cancer Immunocheckpoint inhibitors have shown significant efficacy, but only in a small number of patients with bladder cancer In a new study, Spanish researchers found that higher expression of G9a (EHMT2) was associated with poor clinical outcomes in bladder cancer, and that targeting G9a / DNMT methyltransferase activity with a new inhibitor (cm-272) induced apoptosis and immunogenic cell death The relevant research results were published online in the journal Nature Medicine on July 3, 2019, with the title of "infection of a G9a / DNMT network triggers immune mediated BlackBerry cancer expression" Picture from nature medicine, 2019, DOI: 10.1038/s41591-019-0499-y These researchers confirmed that cm-272 combined with cisplatin resulted in a statistically significant regression of established tumors and metastases by using a transgenic mouse model of aggressive metastatic muscle infiltrating bladder cancer with normal immune activity of quadruple knockout (PTEN loxP / loxP; tr p53 loxP / loxP; RBL 1 - / -) When cm-272 was used in combination with anti-PD-L1 antibody (a kind of immunosuppressive checkpoint inhibitor), this antitumor effect was significantly improved even if cisplatin was not used These effects are related to endogenous anti-tumor immune response and immunogenic cell death, which is related to the transformation of cold immune tumor into hot immune tumor Finally, in a group of bladder cancer patients, increased G9a expression was associated with resistance to PD-1 inhibition In conclusion, these findings provide a new and promising opportunity for the combination of epigenetic inhibitors (such as cm-272) and immunocheckpoint blockade in the treatment of bladder cancer (BIOON Com) reference: Cristina Segovia et al Initiation of a G9a / DNMT network triggers immune mediated BlackBerry cancer registration Nature Medicine, 2019, DOI: 10.1038/s41591-019-0499-y