Attackable weaknesses discovered in liver cancer

Liver cancer is a very common type of tumor. In fact, in many countries it is among the three most commonly detected. In addition to a high incidence, with around one million cases diagnosed each year worldwide, it is a type of tumor that is highly aggressive, with a mortality rate of close to 80% of patients.

Scientists have discovered epigenetic weaknesses in liver cancer that could be used as targets to improve the efficacy of liver cancer treatments.

The group led by Dr. Manel Esteller, director of the Josep Carreras Leukemia Research Institute in Badalona, ​​ICREA Research Professor and Professor of Genetics at the University of Barcelona (UB), has extensive experience in liver cancer research, He was the first to determine the epigenome of this tumor and thus identify the main chemical alterations in DNA that change its genetic expression.

In a new study by the Josep Carreras Leukemia Research Institute, whose main authors are Vanessa Ortiz-Barahona and Marta Soler, it has been possible to unravel key details of the chemical modifications on RNA, the intermediary molecule between genetic information and proteins , the authentic tools of the cell. In this sense, Esteller highlights that “in the last five years, we have contributed to demonstrating that not only the chemical regulation of DNA is altered in cancer but also the ‘marks’ that control the activity of ribonucleic acid (RNA)”.

During the study of which source controls these chemical modifications of the RNA (the so-called epitranscriptome), the researchers found that the NSUN7 gene was clearly altered in liver cancer. “We observed that the NSUN7 gene suffered a loss of functionality in liver tumors and this caused a degradation of its RNA targets, ultimately leading to superactivation of the MYC oncogene”, comments Dr. Esteller.

The activation of oncogenes is usually associated with worse survival, as the results of the study pointed out. However, Esteller comments that “at the same time we verified that the mentioned tumors were more sensitive to drugs that block MYC, such as the so-called bromodomain inhibitors”, opening a new therapeutic avenue that is worth exploring in clinical trials of liver cancer in function of the activation state of NSUN7.

Manel Esteller and Vanessa Ortiz-Barahona. (Photo: Josep Carreras Leukemia Research Institute.)

One unintended consequence of the research is that liver tumors with intact NSUN7 might be more receptive to immunotherapy. Thus, determining the epigenetic situation of NSUN7 in liver cancer patients could have high clinical value and help design a more precise and personalized therapy for the patient.

The study is titled “Epigenetic inactivation of the 5-methylcytosine RNA methyltransferase NSUN7 is associated with clinical outcome and therapeutic vulnerability in liver cancer”. And it has been published in the academic journal Molecular Cancer. (Source: Josep Carreras Leukemia Research Institute)