Genome Engineering

Epigenetic alterations – inherited alterations in genotype or phenotype other than changes in DNA sequence – are linked with cancer. In a paper published in Cancer Discovery, researchers have used epigenetic therapy to target non-small cell lung cancer (NSCLC) by switching silenced genes back on.

In a phase I/II trial, patients with heavily-pretreated recurrent metastatic non–small cell lung cancer were given low doses of azacitidine and entinostat. These are both inhibitors of DNA methylation, and the treatment demethylated four epigenetically-silenced genes known to be linked with lung cancer – these patients had improved progression-free survival. Overall, the patients tolerated the therapy well. Bearing in mind that these are heavily pretreated patients not responding to therapy, two patients showed a positive response to the epigenetic therapy, and four patients responded well to standard anticancer therapies given afterwards.

This could have potential as a treatment alone and in combination with standard chemotherapy in patients with epigenetic changes, and the set of genes has potential as a prognostic and predictive biomarker.

Juergens, R., Wrangle, J., Vendetti, F., Murphy, S., Zhao, M., Coleman, B., Sebree, R., Rodgers, K., Hooker, C., Franco, N., Lee, B., Tsai, S., Delgado, I., Rudek, M., Belinsky, S., Herman, J., Baylin, S., Brock, M., & Rudin, C. (2011). Combination Epigenetic Therapy Has Efficacy in Patients with Refractory Advanced Non-Small Cell Lung Cancer Cancer Discovery DOI: 10.1158/2159-8290.CD-11-0214
Rodriguez-Paredes, M., & Esteller, M. (2011). A Combined Epigenetic Therapy Equals the Efficacy of Conventional Chemotherapy in Refractory Advanced Non-Small Cell Lung Cancer Cancer Discovery DOI: 10.1158/2159-8290.CD-11-0271