Epigenetic hallmarks of cancer unveiled in new research

Josep Carreras Leukaemia Research InstituteOct 1 2024

Cancer mortality has just surpassed cardiovascular disease for the first time ever and one in two men, and one in three women, will be diagnosed with some form of the disease in the US, according to the NIH.

Cancer is a complex pathology involving multiple cellular and molecular alterations that trigger its origin and progression. In the last decade, researchers sought to simplify the problem by providing a common framework to organise research efforts. The main output of this process was the definition of the 14 Hallmarks of Cancer, a common set of abnormalities that are common to all tumours.

Among these Hallmarks are the generation of metastases, the exacerbated growth of cells or the inability to die of the transformed cells. It was believed that these properties were largely due to genetic causes (i.e. mutations), but genetics cannot fully explain the changing and evolutionary nature of human tumours nor their ability to acquire the rapid resistance to therapy. There had to be some other mechanisms involved and the epigenetic control of genetic information seemed a good candidate.

Today, an article published in the journal Cancer Discovery, the publication with most impact of the American Association for Cancer Research (AACR) and led by Dr. Manel Esteller, ICREA Research Professor at the Josep Carreras Leukaemia Research Institute and Chairman of Genetics at the School of Medicine of the University of Barcelona, ​​describes the epigenetic properties that allow the definition of tumours and confer them their incredible ability to adapt and survive in a hostile microenvironment, preventing the death of cancer cells.

"After more than 25 years of studying chemical modifications of DNA and its regulatory proteins, we now have a clearer vision of the epigenetic alterations that most human tumours share", comments Dr. Esteller, and continues "in this article, well-known expert researchers in this field with my coordination have decided to launch these six properties that characterize the epigenetic alterations of tumours in order to improve the diagnosis and prognosis of the disease, as well as its treatment".

According to the expert team, the six epigenetic hallmarks of transformed cells are: the loss of activity of anti-cancer genes due to excessive DNA methylation; the epigenetic reactivation of ancient viral sequences integrated into our genome; a distortion of the modifications of the histone proteins that control gene expression; the remodeling of the three-dimensional structure of the cell nucleus; an epigenetic instability that allows cancer to evolve; and, finally, a "love-hate" relationship with the genetic alterations of cancer where both type of lesions crosstalk and enhance each other.

Cancer epigenetics is still a growing field and, while its foundations are solid, Dr. Esteller points out that "it is important to recognize that these rules are not fixed, and future discoveries using disruptive technologies such as single cell analysis and artificial intelligence can provide additional rules that define the epigenetic hallmarks of cancer."