Epigenetics Enters Cancer Clinical Practice

Josep Carreras Leukaemia Research Institute

In the early 1980s, the first changes in DNA related to a chemical modification called methylation were discovered, followed by the discovery in the mid-1990s of the first tumor suppressor genes inactivated by these modifications of the genetic material. The early 2000s saw the first use of these altered marks as a biomarker of cancer disease, as well as the first uses of drugs against them.

In parallel, the first chemical modifications were detected in proteins called histones, where DNA wraps around them like a pearl necklace. All this "decoration" of DNA and its regulatory proteins define the field of Epigenetics.

Now, on an article published in the journal "CA: A Cancer Journal for Clinicians", Dr. Manel Esteller, Director of the Josep Carreras Leukaemia Research Institute (IJC), ICREA Research Professor and Professor of Genetics at the University of Barcelona, and researcher Dr. Verónica Dávalos explain its impact on the clinical management of cancer patients. This journal is also the organ of expression of the American Cancer Society (ACS) and the scientific journal with the highest Impact Factor according to the Clarivate ranking.

"Epigenetics has gone from being a purely basic research discipline focused on studying how gene expression is controlled to a tool to improve early detection, predict the evolution of the disease and become a target for new treatments", –says Dr. Esteller and adds - "One of the most outstanding aspects of its clinical translation is its use in liquid biopsy, as well as helping in the classification of tumor types, for example to correctly diagnose the types of tumors derived from the brain, skeletal muscles, joints, bones or of unknown origin. But, in addition to this aspect, DNA methylation profiles are approved to determine the efficacy of treatment in brain tumors and other tumor pathologies".

Perhaps one the most attractive aspect for the medical oncologist is the use of epigenetic drugs to treat cancer. There are currently nine drugs against various epigenetic marks (DNA methylation and histone methylation and acetylation) approved for clinical use in various types of leukemia, lymphoma and blood diseases, as well as tumors of the soft tissues. According to Esteller, "these treatments are usually very well tolerated by patients and more than killing the tumor cell, they stop its growth, as if it were a tamed beast".

Epigenetic drugs are a clinical reality and they are already providing benefits for patients, but research continues and, currently, there is a whole new generation of epigenetic drugs in different phases of clinical trials that, alone or combined with immunotherapy, can make a positive difference in many patients.

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