Manel Esteller & Josep M. Llovet

Institut de Recerca contra la Leucèmia Josep Carreras & Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer

Liver cancer is a very common type of tumor, ranking among the top three most commonly detected in many countries. Not only does it have a high incidence, with 1 million cases diagnosed worldwide each year, but it also exhibits high aggressiveness, with a mortality rate close to 80% of patients. The article led by Dr. Manel Esteller in the journal Molecular Cancer shows how the epigenetic inactivation of a gene that modifies the other nucleic acid, RNA, also contributes to generating tumors with a worse prognosis but at the same time provides hopeful targets for new drugs. In the last five years, DR Esteller’s group have contributed to demonstrate that not only is the chemical regulation of DNA altered in cancer, but also the ‘marks’ that control the activity of ribonucleic acid (RNA), which is the one that ultimately generates the proteins that carry out the cells’ work. Studying who controls these chemical modifications of RNA (also called epitranscriptome), the authors found a gene clearly altered in liver cancer. The group observed that the NSUN7 gene underwent a loss of functionality in liver tumors, leading to degradation of its RNA targets, ultimately leading to overactivation of the oncogene MYC. The latter was associated with worse survival of these individuals, but at the same time, the authors found that these tumors were more sensitive to drugs that block MYC, such as so-called bromodomain inhibitors. It would be very interesting to test these compounds in clinical trials for liver cancer in relation to the described NSUN7 states. On the other side, an unforeseen consequence is that those liver tumors with intact NSUN7 may be more receptive to immunotherapy. Thus, determining the epigenetics of NSUN7 in these patients could have a double value for conducting a more precise and personalized therapy.